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1.
Article in English | WPRIM | ID: wpr-921320

ABSTRACT

Objective@#The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors.@*Methods@#Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses.@*Results@#The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ.@*Conclusion@#The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors


Subject(s)
Animals , Antineoplastic Agents/therapeutic use , Cell Proliferation/radiation effects , Combined Modality Therapy , Cytokines/immunology , Fatty Acids, Unsaturated/therapeutic use , Female , Mammary Neoplasms, Experimental/radiotherapy , Rats , Tumor-Associated Macrophages/radiation effects
3.
Article in English | WPRIM | ID: wpr-878337

ABSTRACT

Objective@#To investigate involvement of the aryl hydrocarbon receptor (AhR) in the immunomodulatory effects of cadmium (Cd).@*Methods@#The effect of Cd on AhR activation ( @*Results@#Cd increased @*Conclusion@#AhR signaling is involved in the lung leukocyte proinflammatory cytokine response to Cd. The relevance of the AhR to the cytokine response to Cd provides new insight into the mechanisms of Cd immunotoxicity.


Subject(s)
Animals , Basic Helix-Loop-Helix Transcription Factors/immunology , Cadmium/toxicity , Cytochrome P-450 CYP1A1/immunology , Cytochrome P-450 CYP1B1/immunology , Cytokines/immunology , Environmental Pollutants/toxicity , Male , Rats , Receptors, Aryl Hydrocarbon/immunology
4.
Braz. j. otorhinolaryngol. (Impr.) ; 86(1): 23-29, Jan.-Feb. 2020. tab
Article in English | LILACS | ID: biblio-1089369

ABSTRACT

Abstract Introduction Obstrutive sleep apnea syndrome is characterized by repeated episodes of upper airway obstruction, associated with intermittent hypoxia and hypercapnia, and the main risk factor in childhood is adenotonsillar hypertrophy. The lymphocytes in these structures are responsible for local and systemic immune responses. Objective Verify the levels of the inflammatory markers, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, CRP and α1-GP, in the tonsils of children with and without obstructive sleep apnea syndrome. Methods This cross-sectional prospective study included 34 children with complains of snoring, difficulty breathing during sleep or recurrent tonsillitis. Patients underwent to a complete otorhinolaryngological examination, nasal endoscopy and polysomnography and were divided into two groups with 17 children each: obstructive sleep apnea syndrome group and control group. All underwent an adenotonsillectomy. Cytokines were measured in the collected tonsils (ELISA and Multiplex methods). Results Statistically significant increasing were observed between IL-8 and IL-10 cytokines of patients with obstructive sleep apnea when compared to the control group; also between c-reactive protein and α1-GP of the tonsils cortical region in children with obstructive sleep apnea syndrome when compared with the medullary region. There were no statistically significant differences for the remaining inflammatory mediators. Conclusion After the analysis of the levels of pro and anti-inflammatory markers (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, CRP, α1-GP) in the tonsils, we observed higher levels of markers IL-8 and IL-10 in pediatric patients with obstructive sleep apnea syndrome.


Resumo Introdução A síndrome da apneia obstrutiva do sono é caracterizada por episódios repetidos de obstrução das vias aéreas superiores, associados a hipóxia intermitente e hipercapnia, e o principal fator de risco na infância é a hipertrofia adenotonsilar. Os linfócitos nessas estruturas são responsáveis por respostas imunes locais e sistêmicas. Objetivo Dosar os marcadores inflamatórios, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, PCR e α1-GP, nas tonsilas de crianças com e sem síndrome da apneia obstrutiva do sono. Método Estudamos prospectivamente 34 crianças que se queixavam de ronco, dificuldade para respirar durante o sono ou tonsilites recorrentes. Os pacientes foram submetidos a exame otorrinolaringológico completo, endoscopia nasal e polissonografia e foram divididos em dois grupos com 17 crianças cada: síndrome de apneia obstrutiva do sono e controle. Todos foram submetidos à adenotonsilectomia. As citocinas foram medidas nas tonsilas coletadas (métodos ELISA e Multiplex). Resultados Com diferenças estatisticamente significantes, observou-se aumento das citocinas IL-8 e IL-10 em pacientes com apneia obstrutiva do sono em comparação ao grupo controle, assim como aumento dos níveis de proteína C reativa e de α1-GP na região cortical das tonsilas de crianças portadoras de síndrome da apneia obstrutiva do sono em comparação com a região medular. Não houve diferenças estatisticamente significantes para o restante dos mediadores inflamatórios. Conclusão Após a análise dos níveis de marcadores pró e anti-inflamatórios (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, PCR, α1-GP) nas tonsilas, observamos níveis mais altos de marcadores IL-8 e IL-10 em pacientes pediátricos com síndrome da apneia obstrutiva do sono.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Palatine Tonsil/immunology , Sleep Apnea, Obstructive/immunology , Palatine Tonsil/pathology , Tonsillectomy , C-Reactive Protein/analysis , Orosomucoid/analysis , Biomarkers , Cross-Sectional Studies , Prospective Studies , Cytokines/immunology , Interleukins/analysis , Tumor Necrosis Factor-alpha/analysis , Inflammation/immunology
5.
Int. j. morphol ; 37(4): 1527-1533, Dec. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1040165

ABSTRACT

En órganos dañados, el ácido láctico (AL) modifica la respuesta inmune innata e inflamatoria, induciendo una menor expresión de citoquinas pro-inflamatorias, que provocan, la modulación del reclutamiento de células inmunes. El daño por compresión del nervio isquiático (NI) desencadena una respuesta inflamatoria y un aumento exponencial del infiltrado inflamatorio de células inmunes, produciendo la destrucción de axones y pérdida funcional del nervio. El objetivo de este estudio es evaluar el efecto agudo de la inyección de AL, sobre la proporción de células inmunes en la fase inflamatoria temprana, en el sitio de lesión del NI post compresión. Para ello, se utilizaron 15 ratas machos Sprague Dawley adultas, en tres grupos de compresión nerviosa. Un grupo control, un grupo control negativo con placebo (100 µL PBS) y un grupo experimental con inyección de 100 µL de AL [20mM]. Al tercer día los NI se analizaron histológicamente y se estableció la proporción de células inmunes en el sitio de lesión. Los resultados muestran que la inyección intraneural de AL provoca una disminución en el porcentaje de linfocitos y un aumento en el porcentaje de macrófagos. Este es el primer trabajo de inyección intraneural de AL y demuestra el efecto modulador del AL sobre las células inmunes en el sistema nervioso periférico.


In damaged organs, lactic acid (LA) modifies the innate and inflammatory immune response, inducing a lower expression of pro-inflammatory cytokines, which provoke the modulation of immune cell recruitment. Damage by compression of the sciatic nerve (SN) triggers an inflammatory response and an exponential increase in the inflammatory infiltrate of immune cells, producing the destruction of axons and functional loss of the nerve. The objective of this study is to evaluate the acute effect of the injection of LA, on the proportion of immune cells in the early inflammatory phase, in the site of SN post-compression injury. For this, 15 adult Sprague Dawley rats were used in three groups of nervous compression. A control group, a negative control group with placebo (100 mL PBS) and an experimental group with injection of 100 mL of LA [20mM]. On the third day, the SNs were histologically analyzed and the proportion of immune cells at the injury site was established. The results show that the intraneural injection of LA causes a decrease in the percentage of lymphocytes and an increase in the percentage of macrophages. This is the first work of intraneural injection of LA and demonstrates the modulating effect of LA on immune cells in the peripheral nervous system.


Subject(s)
Animals , Male , Rats , Sciatic Nerve/drug effects , Sciatic Nerve/immunology , Lactic Acid/pharmacology , Nerve Compression Syndromes/pathology , Sciatic Nerve/pathology , Lymphocytes/drug effects , Cytokines/immunology , Cytokines/metabolism , Rats, Sprague-Dawley , Lactic Acid/administration & dosage , Inflammation/immunology , Macrophages/drug effects
6.
Rev. chil. pediatr ; 90(5): 555-558, oct. 2019. graf
Article in Spanish | LILACS | ID: biblio-1058183

ABSTRACT

Resumen: En los últimos años se ha intentado comprender la etiología del Trastorno del Espectro Autista (TEA), evidenciandose que existe una compleja interacción entre factores genéticos y ambientales. Estudios epidemiológicos y en modelos animales sugieren que la activación inmune de la madre durante el embarazo puede asociarse un mayor riesgo de desarrollar TEA en los hijos, destacando el rol de las citoquinas proinflamatorias, los auto-anticuerpos y el rol de la microglia activada en la poda sináptica durante el desarrollo embrionario. Comprender mejor los factores asociados con los Trastornos del Neurodesarrollo permitirá en el futuro desarrollar estrategias de manejo y detección precoz en población de riesgo.


Abstract: Autism Spectrum Disorder (ASD) etiology has been related whit complex interaction between ge netic and environmental factors. In the last years, numerous studies have suggested that maternal immune activation during pregnancy could be related to ASD in the offspring. This relation could be explained by the effects of pro-inflammatory cytokines, autoantibodies and microglial synap tic pruning during early embryonic development. Better understanding of Neurodevelopmental Disorders risk factors will support appropriate strategies of screening and management of risk population.


Subject(s)
Humans , Female , Pregnancy , Pregnancy Complications/immunology , Prenatal Exposure Delayed Effects/immunology , Autism Spectrum Disorder/immunology , Autoantibodies/immunology , Risk Factors , Cytokines/immunology , Microglia/immunology , Autism Spectrum Disorder/etiology
7.
Salvador; s.n; s.n; 2019. 152 p. Ilus, graf, mapas, tab.
Thesis in Portuguese | ColecionaSUS, LILACS, ColecionaSUS, CONASS, SES-BA | ID: biblio-1146484

ABSTRACT

Iintrodução: Os vírus linfotrópico de células T humanas (HTLV) e vírus da hepatite C (HCV) são endêmicos no Brasil. Ambos causam uma infecção persistente, assintomática em alguns casos, sendo o diagnóstico tardio. Estes vírus compartilham algumas vias de transmissão, o que pode favorecer a coinfecção. OBJETIVOS: Determinar a taxa de infecção do HTLV, HCV e coinfecção HTLV/HCV no estado da Bahia. Descrever o perfil de citocinas inflamatórias nos indivíduos coinfectados com HTLV/HCV. Métodos: Um estudo retrospectivo ecológico foi conduzido usando o banco de dados do LACEN ­ Bahia. Todos os testes sorológicos para HTLV e HCV foram selecionados entre as 32 microrregiões da Bahia, no período de 2004 a 2013, constituindo um banco com 602.908 registros únicos. Para a avaliação imune, foram selecionados prospectivamente amostras de 31 indivíduos coinfectados HTLV/HCV e de 27 indivíduos monoinfectados com HCV, recebidas no LACEN para quantificar a carga viral do HCV no período de 2014 a 2016. Foram analisadas as citocinas IFN-γ, TNF-α, IL-10, IL-8 e IL-1. O grupo controle foi formado por 30 indivíduos sadios. Resultados: Foram avaliadas 233.876 amostras para o diagnóstico laboratorial do HTLV. Destas, 1.813 (91,7%) foram positivas para HTLV-1 (prevalência de 0,78%), 58 (2,9%) para HTLV-2 (prevalência de 0,025%) e 107 (5,4%) foram positivas para ambos HTLV-1 e HTLV-2 (prevalência de 0,05%). A taxa de infecção na Bahia foi 0,84% (14,4 casos /100.000 habitantes). A infecção pelo HTLV foi predominante em mulheres (75%) com média de idade de 46 anos. Foram identificados três novos clusters do HTLV, localizados nas regiões Sul, Central e Oeste do estado. Amostras de 247.837 indivíduos foram avaliadas para o diagnóstico laboratorial do HCV. A taxa de infecção do HCV foi de 1,3% que corresponde a 21,2 casos/ 100.000 habitantes. Os homens com idade acima de 55 anos foram os mais acometidos. A cidade de Ipiaú apresentou a maior taxa de infecção para o HCV (112,04 casos/100.000 habitantes). Os genótipos 1 e 3 foram mais prevalentes, seguidos dos genótipos 2, 4 e 5. Para determinar a taxa de coinfecção entre HTLV e HCV amostras de 120.192 indivíduos foram avaliados. A taxa de infecção do HTLV/HCV foi de 14,3% que equivale a 2,8 casos/100.000 habitantes. Os casos de coinfecção HTLV/HCV predominou em homens com média de idade de 59 anos. As maiores taxas foram encontradas em três microrregiões: Salvador, Ilhéus-Itabuna e Porto Seguro. Quanto ao perfil de citocinas, o grupo coinfectados HTLV/HCV teve uma maior tendência a produzir IFN-γ, comparado ao grupo monoinfectado HCV. Houve uma correlação positiva entre os pares IL-1 e IL-8 no grupo coinfectado pelo HTLV/HCV e entre os pares IL-8 - IL10 e INF-γ - IL-10 no grupo monoinfectado pelo HCV. Conclusões: As infecções pelo HTLV e HCV estão disseminadas nas microrregiões do estado Bahia, no entanto a coinfecção HTLV/HCV está concentrada em apenas três microrregiões. A coinfecção HTLV/HCV está associada à produção de IFN-γ, enquanto indivíduos infectados pelo HCV apresentaram correlação positiva entre as citocinas inflamatórias (IL-8 e IFN-γ) e a citocina reguladora IL-10


Subject(s)
Humans , Male , Female , Serologic Tests , Deltaretrovirus Infections , Deltaretrovirus Infections/epidemiology , Cytokines/immunology , Hepacivirus
8.
Rev. Soc. Bras. Med. Trop ; 52: e20190315, 2019. tab, graf
Article in English | LILACS | ID: biblio-1057249

ABSTRACT

Abstract INTRODUCTION: Immunological control of Mycobacterium tuberculosis infection is dependent on the cellular immune response, mediated predominantly by Th1 type CD4+ T cells. Polarization of the immune response to Th2 can inhibit the host immune protection against pathogens. Patients with tuberculosis coinfected with helminths demonstrate more severe pulmonary symptoms, a deficiency in the immune response against tuberculosis, and an impaired response to anti-tuberculosis therapy. METHODS: We evaluated the cellular immune response and the impact of the presence of Ascaris lumbricoides on the immune and clinical response in pulmonary tuberculosis patients. Ninety-one individuals were included in the study: 38 tuberculosis patients, 11 tuberculosis patients coinfected with Ascaris lumbricoides and other helminths, 10 Ascaris lumbricoides patients, and 34 non-infected control individuals. Clinical evolution of pulmonary tuberculosis was studied on 0, 30, 60, and 90 days post-diagnosis of Mycobacterium tuberculosis and Ascaris lumbricoides. Furthermore, immune cells and plasma cytokine profiles were examined in mono/coinfection by Mycobacterium tuberculosis and Ascaris lumbricoides using flow cytometry. RESULTS: There were no statistical differences in any of the evaluated parameters and the results indicated that Ascaris lumbricoides infection does not lead to significant clinical repercussions in the presentation and evolution of pulmonary tuberculosis. CONCLUSIONS: The association with Ascaris lumbricoides did not influence the Th1, Th2, and Th17 type responses, or the proportions of T lymphocyte subpopulations. However, higher serum levels of IL-6 in tuberculosis patients may explain the pulmonary parenchymal damage.


Subject(s)
Humans , Animals , Male , Female , Adult , Young Adult , Ascariasis/immunology , Tuberculosis, Pulmonary/immunology , Interleukin-6/blood , Ascaris lumbricoides , Ascariasis/complications , Time Factors , Tuberculosis, Pulmonary/complications , Antibodies, Helminth/blood , Case-Control Studies , Cytokines/immunology , Cytokines/blood , Interleukin-6/immunology , Disease Progression , Coinfection , Flow Cytometry , Middle Aged
9.
Rev. Soc. Bras. Med. Trop ; 52: e20190386, 2019. tab, graf
Article in English | LILACS | ID: biblio-1057241

ABSTRACT

Abstract INTRODUCTION: Chronic chagasic cardiopathy (CCC) is essentially a dilated cardiomyopathy in which a subacute, but constant chronic inflammatory process causes progressive destruction of the heart tissue. The action of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and anti-inflammatory cytokines, like interleukin IL-10 and IL-17, plays a fundamental role in the immunopathogenesis and evolution of disease. Early anti-congestive therapy, aimed at changing the morbidity and mortality rate, has been shown to reduce disease progression and to alter patients' immune response pattern. METHODS: This cross-sectional study aimed to evaluate the profile of Th1 and Th17 cytokines and IL-17, TNF-α, and IFN-γ expressions in different stages of CCC. Forty patients affected by chronic Chagas disease were divided into different groups according to the stage of the pathology. In agreement with the Brazilian consensus on Chagas disease, patients were classified as presenting an undetermined form, a cardiac form and a digestive form. Serum IFN-γ, TNF-α, IL-10, and IL-17 were evaluated. RESULTS: Lower serum IFN-γ concentrations were detected in patients receiving angiotensin-converting enzyme inhibitors (p = 0.0182), but not in those using angiotensin receptor blockers (p = 0.0783). Patients using amiodarone and aldosterone antagonist presented higher serum TNF-α concentrations (p = 0.0106 and 0.0187, respectively). IL-10 and IL-17 levels did not differ between the study groups (p = 0.7273 and p = 0.6697, respectively). CONCLUSIONS: These results suggest that the cytokine profile and disease progression are altered by anti-congestive medications commonly prescribed for CCC.


Subject(s)
Humans , Male , Female , Adult , Aged , Chagas Cardiomyopathy/immunology , Cytokines/blood , Chagas Cardiomyopathy/drug therapy , Chagas Cardiomyopathy/blood , Chronic Disease , Cross-Sectional Studies , Cytokines/immunology , Disease Progression , Middle Aged
10.
An. bras. dermatol ; 93(6): 829-835, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-973620

ABSTRACT

Abstract: Background: Allergic contact dermatitis to ion nickel (Ni+2) is an inflammatory dermatosis, common in industrialized countries. It involves the activation of nickel-specific T-cells, followed by proliferation and induction of a mixed profile of both proinflammatory and regulatory cytokines, suggesting that several T-cell subtypes (helper - Th and cytotoxic - Tc) are involved. A broader understanding of the cytokine profile may lead to new therapeutic approaches. Objectives: This study aimed to analyze the cytokines TNF-α, INF-γ, IL-2, IL-4, IL-10, IL-13, IL-17 and IL-23 using the immunohistochemistry technique in order to try to identify their prevalence in chronic and acute eczema of patients with allergic contact dermatitis to Ni+2. Methods: We performed an immunohistochemical study for eight cytokines in 20 patients with Ni+2 allergic contact dermatitis, biopsied at the site of chronic eczema, triggered by the patient's daily contact with Ni+2, and at the site of acute eczema caused by nickel sulfate, 48 hours after applying the contact test. Results: The stained samples showed positive results for the eight cytokines studied. TNF-α, IFN-γ, IL-4, IL-13 and IL-17 had a higher prevalence in chronic eczema, IL-2 and IL-23 in acute eczema, and IL-10 presented a similar prevalence in both acute and chronic eczema. However, these prevalences were statistically significant only for IL-4 and IL-13. Study Limitations: Small sample size. Conclusions: In chronic and acute eczema, we observed the presence of a mixed cytokine profile of the T cell subtypes (Th/Tc), suggesting that the responses are expressed at the same time.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Cytokines/analysis , Interleukins/analysis , Interferon-gamma/analysis , Tumor Necrosis Factor-alpha/analysis , Dermatitis, Allergic Contact/immunology , Nickel/adverse effects , Biopsy , Immunohistochemistry , Acute Disease , Chronic Disease , Prospective Studies , Cytokines/immunology , Interleukins/immunology , Interferon-gamma/immunology , Tumor Necrosis Factor-alpha/immunology , Dermatitis, Allergic Contact/etiology , Dermatitis, Allergic Contact/pathology , Nickel/immunology
11.
J. pediatr. (Rio J.) ; 94(5): 546-553, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-975984

ABSTRACT

Abstract Objective: There is evidence of an important role of immune system changes in the triggering and maintenance of idiopathic nephrotic syndrome (INS). The aim of this study was to investigate the expression of cytokines in lymphocyte populations of patients with INS in comparison to healthy individuals, according to proteinuria. Methods: This cross-sectional study included 44 patients with INS and eight healthy children, matched for age and sex (controls). Patients were subdivided according to proteinuria: persistent proteinuria or partial remission (PP ≥ 300 mg/24 h, n = 17) and low proteinuria or complete remission (LP < 300 mg/24 h, n = 27). Ex vivo analysis of peripheral blood leukocytes by flow cytometry was performed using surface markers for T-lymphocytes, TCD4, TCD8, natural killer (NK) cells, NKT, and B-lymphocytes. Frequencies of intracellular cytokines were analyzed in these cells. Results: The frequencies of B-lymphocytes, NK cells, and NKT cells were lower in INS than in controls, whereas INS patients had a higher frequency of CD4+tumor necrosis factor (TNF)-α+ cells than controls. Cytotoxic-T-lymphocytes expressing IFN-γ were lower in INS than in controls. Patients with PP showed higher frequencies of CD4-T-lymphocytes expressing IFN-γ and TNF-α than controls. CD8-lymphocytes expressing TNF-α were increased in PP group when compared with LP and controls, while CD8+interferon (IFN)-γ+ cells were lower than in LP and in controls. Conclusion: Regardless the level of proteinuria, INS patients had increased expression of TNF-α in CD4-lymphocytes and reduced expression of IFN-γ in CD8-lymphocytes. Persistence of proteinuria was associated with higher levels of inflammatory markers.


Resumo Objetivo Há comprovação do importante papel das alterações no sistema imunológico no desencadeamento e manutenção da síndrome nefrótica idiopática (SNI). O objetivo deste estudo foi investigar a expressão das citocinas em populações de linfócitos de pacientes com SNI em comparação a indivíduos saudáveis e de acordo com a proteinúria. Métodos Este estudo transversal incluiu 44 pacientes com SNI e oito crianças saudáveis, pareados por idade e sexo (controles). Os pacientes foram subdivididos de acordo com a proteinúria: proteinúria persistente ou remissão parcial (PP ≥ 300 mg/24 h, n = 17) e proteinúria baixa ou remissão completa (PB < 300 mg/24 h, n = 27). A análise ex vivo de leucócitos no sangue periférico por citometria de fluxo foi feita utilizando marcadores de superfície para linfócitos T, TCD4, TCD8, células natural killer (NK), linfócitos NKT e B. As frequências das citocinas intracelulares foram analisadas nessas células. Resultados A frequência dos linfócitos B, células NK e células NKT foi menor em pacientes com SNI do que nos controles, ao passo que os pacientes com SNI apresentaram maior frequência de células CD4+fator de necrose tumoral (TNF)-α+ do que nos controles. Os linfócitos T citotóxicos que expressam interferon (IFN)-γ foram menores nos pacientes com SNI do que nos controles. Os pacientes com PP mostraram maiores frequências de linfócitos T CD4 que expressam IFN-γ e TNF-α que os controles. Os linfócitos CD8 que expressam TNF-α apresentaram aumento no grupo com PP, em comparação aos com PB e os controles, apesar de as células CD8+IFN-γ+ serem mais baixas nos pacientes com PB e nos controles. Conclusão Com relação ao nível de proteinúria, os pacientes com SNI apresentaram aumento na expressão de TNF-α nos linfócitos CD4 e expressão reduzida de IFN-γ nos linfócitos CD8. A persistência da proteinúria foi associada a maiores níveis de marcadores inflamatórios.


Subject(s)
Humans , Male , Female , Child , Adolescent , Proteinuria/etiology , Killer Cells, Natural/immunology , T-Lymphocytes/immunology , Cytokines/immunology , Nephrotic Syndrome/immunology , Proteinuria/immunology , Proteinuria/blood , Biomarkers , Case-Control Studies , Cross-Sectional Studies , Cytokines/blood , Disease Progression , Flow Cytometry , Leukocyte Count , Nephrotic Syndrome/complications , Nephrotic Syndrome/blood
12.
Braz. j. biol ; 78(2): 271-280, May-Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-888875

ABSTRACT

Abstract Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.


Resumo Sepse induz uma resposta inflamatória sistêmica grave podendo resultar em disfunção de múltiplos órgãos e morte. Pesquisas utilizando uma proteína derivada do látex natural de Hevea brasiliensis (seringueira), denominada Hev b 13 tem demonstrado importantes efeitos anti-inflamatórios, mas nenhum dado foi publicado dos seus efeitos na sepse. O objetivo deste estudo foi investigar os efeitos da Hev b 13 na resposta inflamatória e na lesão pulmonar de ratos com sepse. Ratos machos da linhagem Wistar foram submetidos a ligação e perfuração do ceco (LPC), randomizados em grupos e tratados com as doses 0,5/2,0/3,0 mg/Kg de Hev b 13 subcutâneo. Após subdividiu-se os animais em três pontos diferentes de tempo (1, 6 e 24 horas após os tratamentos) para coleta de amostras sanguíneas e eutanásia com remoção dos órgãos. Contagem total e diferencial de leucócitos, dosagem de citocinas e avaliação histológica foram analisadas. O tratamento com a Hev b 13 resultou em diminuição significativa de leucócitos totais e diferenciais bem como suprimiu a produção de TNF-α e IL-6, associado ao aumento de IL-10 e IL-4 no plasma e tecido pulmonar. Além disso, reduziu as alterações morfológicas e patológicas encontradas nos pulmões, incluindo infiltrado de neutrófilos, edema e espessamento alveolar. Este estudo concluiu que a Hev b 13 tem efeitos anti-inflamatórios e atenua lesões pulmonares em ratos com sepse, apresentando potencialidades para aplicabilidade clínica.


Subject(s)
Animals , Male , Rats , Plant Proteins/pharmacology , Antigens, Plant/pharmacology , Lung/drug effects , Lung/immunology , Lung/metabolism , Lung Diseases/metabolism , Plant Proteins/administration & dosage , Random Allocation , Cytokines/immunology , Cytokines/metabolism , Cytokines/blood , Rats, Wistar , Sepsis/metabolism , Disease Models, Animal , Antigens, Plant/administration & dosage , Lung Diseases/immunology
13.
An. bras. dermatol ; 93(2): 242-250, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-887186

ABSTRACT

Abstract: Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.


Subject(s)
Humans , Skin/immunology , T-Lymphocytes/immunology , Dermatitis, Allergic Contact/immunology , Immunity, Innate/immunology , Cytokines/immunology , T-Lymphocytes, Regulatory/immunology , Toll-Like Receptors/immunology
14.
Braz. j. infect. dis ; 22(2): 142-145, Mar.-Apr. 2018. tab
Article in English | LILACS | ID: biblio-1039213

ABSTRACT

ABSTRACT The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles.


Subject(s)
Humans , Female , Adult , HIV Infections/immunology , Cytokines/immunology , HIV-1 , HIV Long-Term Survivors , CD4-Positive T-Lymphocytes/immunology , HIV Infections/blood , HIV Infections/virology , Th2 Cells/immunology , Th1 Cells/immunology , CD8-Positive T-Lymphocytes/immunology , Viral Load , Antiretroviral Therapy, Highly Active , Immunity, Cellular/immunology
15.
Pesqui. bras. odontopediatria clín. integr ; 18(1): 4123, 15/01/2018. tab, graf
Article in English | LILACS, BBO | ID: biblio-966911

ABSTRACT

Objective: To evaluate the effect of repeated removal and placement of abutments during prosthetic stages on increasing proinflammatory cytokine levels around dental implants. Material and Methods: All the patients with dental implants, referring to the prosthodontics private office during a 3-month period, were examined in relation to the health of the implants and included in the present study based on inclusion criteria; the patients had a multi-unit abutment on one side of the jaw and a conventional healing abutment on the implant on the other side of the jaw. Samples of gingival crevicular fluid were taken from all the eligible subjects for immunological analyses. The samples were taken from the sulcus around each implant in each subject. The samples were sent to the immunology laboratory for determination of IL-6 and IL-1ß proinflammatory cytokines with the use of an ELISA kit. Data were analyzed with SPSS 16 and Descriptive statistics and T-test was used. Statistical significance was set at p<0.05. Results: The results showed that the mean concentrations of IL-1ß and IL-6 in the group with multi-unit abutment were less than those in the conventional abutment group. In addition, comparison of the means of IL-6 and IL-1ß concentrations showed that in both groups the concentration of IL-6 was higher than that of IL-1ß. Conclusion: The use of multi-unit abutments resulted in less inflammation compared to the use of conventional two-segment abutments, which require repeated removal and placement during the prosthetic stage.


Subject(s)
Humans , Dental Implants , Cytokines/immunology , Gingival Crevicular Fluid , Gingiva/injuries , Data Interpretation, Statistical , Clinical Study , Iran
16.
Braz. j. med. biol. res ; 51(5): e6773, 2018. graf
Article in English | LILACS | ID: biblio-889077

ABSTRACT

Bacterial infections occur worldwide and are a major public health problem. Among pathogens, Staphylococcus aureus is the main causative agent of bacterial diseases in the world. This study aimed to evaluate which components of the immune system could act protectively against a S. aureus infection in intradermally immunized mice. C57BL/6 and A/j mice were immunized intradermally with S. aureus inactivated by heat and then challenged with viable strains in an air pouch model. At 6, 12, and 24 h after the challenge, euthanasia was performed, and the cellular profile of the inflammatory infiltrate, cytokines, and the bacterial load were evaluated in the air pouch lavages. Immunized mice demonstrated that the intradermal immunization with S. aureus promoted protection in C57BL/6 mice by reducing the bacterial, which was correlated with increased serum concentration of IgG antibodies (IgG1 and IgG2a) against S. aureus. The increase in IgG2a antibody levels was correlated with a decrease of bacterial load in intradermally immunized C57BL/6 mice, along with production of IL-17A at the inflammation site, as well as IgG1consumption. Similar results were not found in the A/j lineage. In conclusion, a vaccine against S. aureus should focus more on the individual characteristics of the host because it is a determinant factor for the success of the immunization.


Subject(s)
Animals , Mice , Antibodies, Bacterial/immunology , Methicillin-Resistant Staphylococcus aureus/immunology , Staphylococcal Infections/prevention & control , Staphylococcal Vaccines/immunology , Bacterial Load , Cytokines/immunology , Disease Models, Animal , Immunoglobulin G/immunology , Mice, Inbred C57BL , Staphylococcal Infections/immunology , Staphylococcal Vaccines/administration & dosage , Time Factors
17.
Mem. Inst. Oswaldo Cruz ; 112(8): 561-568, Aug. 2017. graf
Article in English | LILACS | ID: biblio-894865

ABSTRACT

BACKGROUND Visceral leishmaniasis (VL) caused by Leishmania infantum is characterised by the loss of the ability of the host to generate an effective immune response. Chemokines have a direct involvement in the pathogenesis of leishmaniasis, causing a rapid change in the expression of these molecules during infection by Leishmania. OBJECTIVES Herein, it was investigated the role of CXCL10 in controlling infection by L. infantum. METHODS RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10 production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice were infected and treated or not with CXCL10 (5 μg/kg) at one, three and seven days of infection. Parasite load, IFN-g, IL-4, TGF-β and IL-10 were evaluated one, seven and 23 days post treatment. FINDINGS In vitro, CXCL10 reduced parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four weeks after infection, representing a higher decrease in the number of parasites in these organs, also induced IFN-γ at day 23 after treatment, correlating with the decrease in parasite load, and reduced IL-10 and TGF-β. MAIN CONCLUSIONS This study suggests a partial protective role of CXCL10 against L. infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10 and TGF-β. These data may provide information for the development of new approaches for future therapeutic interventions for VL.


Subject(s)
Animals , Male , Mice , Organ Size/physiology , Interleukin-4/biosynthesis , Interleukin-10/biosynthesis , Leishmania infantum , Chemokine CXCL10/therapeutic use , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/drug therapy , Liver/pathology , Macrophages/drug effects , Cytokines/immunology , Interferon-gamma/analysis , Mice, Inbred BALB C
18.
Mem. Inst. Oswaldo Cruz ; 112(6): 458-468, June 2017. tab, graf
Article in English | LILACS | ID: biblio-841802

ABSTRACT

ABSTRACT BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features. METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN CONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.


Subject(s)
Humans , Antiviral Agents/pharmacology , Plant Extracts/pharmacology , Cell Survival/drug effects , Cytokines/drug effects , Cytokines/immunology , Chemokines/drug effects , Chemokines/immunology , Uncaria/chemistry , Dengue/physiopathology , Dengue/immunology , Dengue/virology , Dengue Virus/drug effects , Dengue Virus/immunology , Antigens, Viral/drug effects , Antigens, Viral/immunology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry
19.
Braz. j. otorhinolaryngol. (Impr.) ; 83(1): 66-72, Jan.-Feb. 2017. tab, graf
Article in English | LILACS | ID: biblio-839397

ABSTRACT

Abstract Introduction Eosinophilic and noneosinophilic Nasal polyps (NPs) are different subtypes of NPs and require different treatment methods. Objective To compare the histologic characteristics, mRNA and protein expression between Nasal Polyps with and without eosinophilia. Methods NPs tissues were obtained from eighty-six NPs patients during surgery. Eosinophilic and noneosinophilic NPs were distinguished according to immunochemical results of the specimen. The histological, mRNA and protein expression features were compared between the two groups. Results In eosinophilic NPs, we observed a significantly higher GATA-3, IL-5, IL-4, IL-13 mRNA and protein expression. In noneosinophilic NPs, IL-17, IL-23 and RORc mRNA and protein expression were increased. Immunohistochemistry tests showed, more mast cells and less neutrophils in eosinophilic NPs compared with noneosinophilic NPs. Eosinophilic NPs patient presented more severe symptom scores when compared to noneosinophilic NPs. Conclusion We demonstrate for the first time that Th2 is the predominant reaction in eosinophilic NPs while Th17 is the predominant reaction in noneosinophilic NPs. Our study may provide new treatment strategy for NPs.


Resumo Introdução Pólipos nasais (PNs) eosinofílicos e não eosinofílicos são diferentes subtipos de PNs e requerem diferentes métodos de tratamento. Objetivo Comparar as características histológicas e a expressão de mRNAs e proteínas entre PNs com e sem eosinofilia. Método Amostras de PNs foram obtidos de 86 pacientes durante a cirurgia. PNs eosinofílicos e não eosinofílicos foram diferenciados segundo os resultados imunoistoquímicos de cada amostra. As características histológicas e de expressão de mRNAs e de proteínas foram comparadas entre os dois grupos. Resultados Em PNs eosinofílicos, observamos uma expressão significativamente maior dos mRNAs e proteínas GATA-3, IL-5, IL-4 e IL-13. Nos PNs não eosinofílicos, aumentou a expressão dos mRNAs e das proteínas IL-17, IL-23 e RORc. Nos testes imunoistoquímicos, observamos maior número de mastócitos e menor número de neutrófilos nos PNs eosinofílicos, em comparação com PNs não eosinofílicos. Os pacientes com PNs eosinofílicos obtiveram escores de sintomas mais graves vs. PNs não eosinofílicos. Conclusão Demonstramos, pela primeira vez, uma reação Th2 predominante em PNs eosinofílicos e uma reação Th17 predominante em PNs não eosinofílicos. Nosso estudo pode proporcionar novas estratégias terapêuticas para a rinossinusite crônica.


Subject(s)
Humans , Male , Female , Adult , Sinusitis/immunology , Rhinitis/immunology , Nasal Polyps/immunology , Eosinophils/immunology , Sinusitis/complications , Transcription Factors , Severity of Illness Index , RNA, Messenger/metabolism , Immunohistochemistry , Rhinitis/complications , Nasal Polyps/complications , Nasal Polyps/metabolism , Nasal Polyps/pathology , Chronic Disease , Cytokines/immunology , T-Lymphocytes, Helper-Inducer/immunology , Eosinophilia/complications , Eosinophilia/metabolism , Eosinophilia/pathology , Real-Time Polymerase Chain Reaction
20.
Braz. j. med. biol. res ; 50(3): e5625, 2017. tab, graf
Article in English | LILACS | ID: biblio-839261

ABSTRACT

This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood. ELISA was used to measure serum levels of MCP-1, NF-κB, IFN-γ, IL-2, IL-4, and IL-10. Flow cytometry was adopted to assess the distributions of CD4+, CD8+ lymphocytes and CD4+ CD25+ Foxp3 lymphocyte subsets. Compared with the sham and blank groups, the mRNA and protein expressions of MCP-1 and NF-κB in the experimental group were significantly increased. The experimental group had lower serum levels of IL-2 and IFN-γ and higher serum level of IL-10 than the sham and blank groups. In comparison to the sham and blank groups, CD4+ T lymphocyte subsets percentage, CD4+/CD8+ ratio and CD4+ CD25+ Foxp3+ Tregs subsets accounting for CD4+ lymphocyte in the experimental group were lower, while percentage of CD8+ T lymphocyte subsets was higher. Our study provided evidence that higher expression of MCP-1 and NF-κB may be associated with decreased immune function of spinal tuberculosis, which can provide a new treatment direction for spinal tuberculosis.


Subject(s)
Animals , Male , Rabbits , Chemokine CCL2/metabolism , Immunity, Cellular/immunology , NF-kappa B/metabolism , Tuberculosis, Spinal/immunology , Blotting, Western , Chemokine CCL2/blood , Cytokines/blood , Cytokines/immunology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , NF-kappa B/blood , Real-Time Polymerase Chain Reaction
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