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Rev. bras. med. esporte ; 27(spe2): 54-57, Apr.-June 2021. graf
Article in English | LILACS | ID: biblio-1280093


ABSTRACT Soft tissue injury is the most common disease in orthopedics, and it is also the most easily neglected disease in sports. Without timely and effective treatment, it is easy to develop into malignant strain and seriously affect life and sports. In view of this, the aim of this study is to analyze the effect and mechanism of traditional Chinese medicine gel in treating such injuries in the light of the characteristics of sports-related soft tissue injury. The right gastrocnemius muscle injury was simulated in 36 adult male rats. Chinese medicine gel and tincture were used to treat it. The contents of interleukin, alanine aminotransferase, blood urea nitrogen and prostaglandin E2 in the blood of rats under different courses of treatment were analyzed to explore recovery in four rats. The results showed that the levels of interleukin and prostaglandin E2 in the blood of rats treated with drugs were significantly lower than those in the control group (p<0.05), indicating that both drugs have obvious therapeutic effects on soft tissue injury. The content of interleukin in the blood of the Chinese medicine gel group was slightly lower than that of the tincture group, indicating that the Chinese medicine gel could affect the recovery of soft tissue injury by affecting leukocyte interleukin. This result is helpful in the treatment of soft tissue injury in sports and to further improve the therapeutic effect of traditional Chinese medicine gel.

RESUMO A lesão dos tecidos moles é a doença mais comum na ortopedia, e é também a doença mais facilmente negligenciada nos esportes. Sem tratamento ágil e eficaz, facilmente evolui para luxações malignas, afetando seriamente a vida e a prática de esportes. Em vista disso, o objetivo deste estudo é analisar o efeito e o mecanismo do gel da medicina tradicional chinesa no tratamento de tais lesões, com base nas características da lesão dos tecidos moles relacionada à prática esportiva. Estimulou-se lesão do músculo gastrocnêmio direito em 36 ratos adultos. O gel e a tintura chinesa foram usados para o tratamento. Foram analisados os conteúdos de interleucina, alanina aminotransferase, ureia sanguínea azoto e prostaglandina E2 no sangue dos ratos sob diferentes tratamentos, de modo a explorar a recuperação de quatro ratos. Os resultados mostraram que os níveis de interleucina e prostaglandina E2 no sangue dos ratos tratados com medicamentos eram significativamente inferiores aos do grupo controle (p<0.05), indicando que ambos os fármacos têm efeitos terapêuticos óbvios sobre lesões dos tecidos moles. O teor de interleucina no sangue do grupo gel chinês medicinal mostrou-se ligeiramente inferior ao do grupo tintura, indicando que o gel medicinal chinês pode afetar a recuperação da lesão nos tecidos moles, afetando o leucócito interleucina. Este resultado é útil para o tratamento de lesões dos tecidos moles relacionadas à prática esportiva e para melhorar ainda mais o efeito terapêutico do gel da medicina chinesa tradicional.

RESUMEN La lesión de los tejidos blandos es la enfermedad más común en la ortopedia, y es también la enfermedad más fácilmente descuidada en los deportes. Sin tratamiento ágil y eficaz, fácilmente evolucionan a luxaciones malignas, afectando seriamente la vida y la práctica de deportes. En vista de eso, el objetivo de este estudio es analizar el efecto y el mecanismo del gel de la medicina tradicional china en el tratamiento de tales lesiones, con base en las características de la lesión de los tejidos blandos relacionada a la práctica deportiva. Se estimuló lesión del músculo gastrocnemio derecho en 36 ratones adultos. El gel y la tintura china fueron usados para el tratamiento. Fueron analizados los contenidos de interleucina, alanina aminotransferasa, urea sanguínea, nitrógeno y prostaglandina E2 en la sangre de los ratones bajo diferentes tratamientos, de modo de explorar la recuperación de cuatro ratones. Los resultados mostraron que los niveles de interleucina y prostaglandina E2 en la sangre de los ratones tratados con medicamentos eran significativamente inferiores a los del grupo control (p<0.05), indicando que ambos fármacos tienen efectos terapéuticos obvios sobre lesiones de los tejidos blandos. El tenor de interleucina en la sangre del grupo gel chino medicinal se mostró ligeramente inferior al del grupo tintura, indicando que el gel medicinal chino puede afectar la recuperación de la lesión en los tejidos blandos, afectando el leucocito interleucina. Este resultado es útil para el tratamiento de lesiones de los tejidos blandos relacionadas a la práctica deportiva y para mejorar aún más el efecto terapéutico del gel de la medicina china tradicional.

Animals , Rats , Ointments/therapeutic use , Muscle, Skeletal/injuries , Medicine, Chinese Traditional , Athletic Injuries/drug therapy , Blood Urea Nitrogen , Dinoprostone/blood , Interleukins/blood , Treatment Outcome , Alanine Transaminase/blood , Disease Models, Animal
Rev. Assoc. Med. Bras. (1992) ; 66(11): 1583-1588, Nov. 2020. tab
Article in English | LILACS, SES-SP | ID: biblio-1143646


SUMMARY OBJECTIVE: The role of interleukins, such as IL-17 and IL-34, in the pathogenesis of autoimmune diseases has been established in the literature. In the current study, we aimed to identify the concentrations of IL-17 (IL-17A, IL-17F) and IL-34 in the cerebrospinal fluid (CSF) of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and acute inflammatory demyelinating neuropathy (AIDN). METHODS: We included in this study 8 patients with CIDP (none of them receiving immunomodulatory or immunosuppressant therapy), 7 patients with Guillain-Barre syndrome (GBS, AIDN), and 7 control subjects. The CIDP and AIDN diagnoses were made by clinical evaluation and electrophysiological investigations according to international criteria. CSF samples were obtained appropriately, and the levels of IL-17A, IL-17F, and IL-34 were measured by ELISA kits. RESULTS: The concentrations of IL-17A, IL-17F, and IL-34 were higher in those with CIDP and AIDN compared to the controls (p=0.005, p=0.01, and p=0.001, respectively). While IL-34 levels were significantly higher in AIDN patients than in CIDP patients (p=0.04), there were no significant differences between the AIDN and CIDP groups with regard to the levels of IL-17A and IL-17F (p=0.4 and p=0.2, respectively) CONCLUSION: Our results indicate that IL-17A, IL-17F, and IL-34 levels may have a role in CIDP and AIDN. Furthermore, the difference in the IL-34 levels of patients with AIDN and CIDP may indicate an important difference between the pathogenesis of these two sets of the disease.

RESUMO OBJETIVO: O papel das interleucinas, como IL-17 e IL-34, na patogênese da doença auto-imune foi estabelecido na literatura. No presente estudo, objetivamos identificar as concentrações de IL-17 (IL-17A, IL-17F) e IL-34 no líquido cefalorraquidiano (LCR) de pacientes com polineuropatia desmielinizante inflamatória crônica (CIDP) e neuropatia desmielinizante inflamatória aguda (AIDN). MÉTODOS: incluímos neste estudo 8 pacientes com CIDP (nenhum deles recebendo terapia imunomoduladora ou imunossupressora), 7 pacientes com síndrome de Guillain-Barre (GBS, AIDN) e 7 indivíduos controle. Os diagnósticos CIDP e AIDN foram feitos por avaliação clínica e investigações eletrofisiológicas de acordo com critérios internacionais. As amostras de LCR foram obtidas adequadamente e os níveis de IL-17A, IL-17F e IL-34 foram medidos através de kits ELISA. RESULTADOS: As concentrações de IL-17A, IL-17F e IL-34 foram maiores naqueles com CIDP e AIDN em comparação aos controles (p = 0,005, p = 0,01 ep = 0,001, respectivamente). Enquanto os níveis de IL-34 foram significativamente mais altos nos pacientes com AIDN do que nos pacientes com CIDP (p = 0,04), não houve diferenças significativas entre os grupos com AIDN e CIDP em relação aos níveis de IL-17A e IL-17F (p = 0,4 ep = 0,2, respectivamente) CONCLUSÃO: Nossos resultados indicam que os níveis de IL-17A, IL-17F e IL-34 podem ter um papel no CIDP e no AIDN. Além disso, a diferença nos níveis de IL-34 de pacientes com AIDN e CIDP pode indicar uma diferença importante entre a patogênese desses dois conjuntos de doenças.

Humans , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Enzyme-Linked Immunosorbent Assay , Interleukins , Interleukin-17 , Guillain-Barre Syndrome
Rev. bras. cir. cardiovasc ; 35(5): 697-705, Sept.-Oct. 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1137330


Abstract Objective: To investigate the association between interleukin-35 (IL-35) levels and single nucleotide polymorphisms (rs3761548, rs3761547) of the FoxP3 gene in coronary artery bypass grafting (CABG) patients. Methods: We conducted a prospective study including 140 patients, who were scheduled for elective isolated on-pump CABG with cardiopulmonary bypass (CPB) from January 2017 to September 2018 in the Jorjani heart center. Blood samples were collected before and 12 hours after the operation. Serum levels of IL-35 were measured by enzyme-linked immunosorbent assay and the pattern of genetic variations was assessed using single specific primer-polymerase chain reaction. Results: The serum concentrations of IL-35 after surgery were significantly higher than pre-surgery levels (18.4±8.3 vs. 9.89±3.2, respectively, P=0.002). There was no significant association between genotype frequencies of rs3761548 and rs3761547 and elevated IL-35 levels (P>0.05). There were significant associations between IL-35 levels and preoperative variables, including age (r=-0.34, P=0.047) and body mass index (r=-0.41, P=0.045), and intraoperative variables, including CPB time (r=0.4, P=0.02) and mean arterial pressure (r=-0.38, P=0.046), in carriers of the rs3761548 AA genotype. Conclusion: Serum IL-35 concentrations were significantly increased in CPB patients, which may contribute to the post-CPB compensatory anti-inflammatory response syndrome. IL-35 increased levels were not influenced by FoxP3 promoter polymorphisms (rs3761548, rs3761547).

Humans , Male , Female , Cardiopulmonary Bypass , Coronary Artery Bypass , Interleukins/blood , Forkhead Transcription Factors/blood , Prospective Studies , Interleukins/genetics , Polymorphism, Single Nucleotide , Forkhead Transcription Factors/genetics
Rev. argent. reumatolg. (En línea) ; 31(3): 40-50, set. 2020. ilus, tab
Article in Spanish | LILACS, BINACIS | ID: biblio-1149675


Introducción: La artritis reumatoidea se caracteriza por inflamación de la membrana sinovial debido al infiltrado de células inmunitarias que secretan citocinas relacionadas a perfil Th17 como IL-22 e IL-6. La dinámica de estas citocinas durante el tratamiento permanece incomprendida. El objetivo fue evaluar los niveles séricos y en líquido sinovial (LS) de IL-22 e IL-6, correlacionarlos con diferentes parámetros bioquímicos y clínicos y medir sus cambios post-tratamiento. Material y métodos: Se estudiaron 77 pacientes con AR y 30 controles. A 30 pacientes se los evaluó nuevamente luego de 3 meses de tratamiento y a 12 se les extrajo LS. Se midió VSG, PCR, FR, anti-CCPhs, IL-22 e IL-6. Se evaluó la actividad con DAS28 y respuesta al tratamiento con criterios EULAR. Resultados: IL-22 e IL-6 fueron similares entre pacientes y controles. Sus niveles disminuyeron luego del tratamiento, principalmente en pacientes respondedores. IL-22 fue menor e IL-6 mayor en LS que en sangre. IL-6 correlacionó positivamente con PCR y anti-CCPhs. Los niveles de VSG, PCR y DAS28 fueron mayores en pacientes con valores dosables de IL-6 que en no dosables. Conclusión: En pacientes con valores basales dosables de IL-22 e IL-6, los niveles de estas citocinas podrían utilizarse como marcador adicional de respuesta al tratamiento.

Introduction: Rheumatoid arthritis is characterized by synovium inflammation due to the infiltration of immune cells that secrete Th17 cytokines like IL-22 and IL-6. The dynamics of these cytokines during the treatment remain unknown. The aim of this study was to evaluate the levels of IL-22 and IL-6 serum and synovial fluid (SF) in correlation with different biochemical and clinical parameters and treatment-associated changes. Material and methods: Seventy-seven RA patients and 30 controls were recruited. Thirty patients were evaluated after 3 months of treatment and SF was collected of 12 patients. ESR, CRP, RF, anti-CCP hs, IL-22 e IL-6 were measured. DAS28 was used to assess disease activity and response to treatment followed EULAR criteria. Results: There were not differences in serum IL-22 and IL-6 levels between patients and controls. Cytokine levels decreased after treatment, mainly in responder patients. IL-22 was decreased and IL-6 was increased in SF compared to serum. IL-6 correlated positively with CRP and anti-CCPhs. ESR, CRP and DAS28 were increased in patients with detectable IL-6 compared to those with undetectable IL-6. Conclusion: In patients with detectable serum IL-22 and IL-6 levels before treatment initiation, follow-up of cytokine levels could be an useful additional tool to evaluate treatment response.

Arthritis, Rheumatoid , Therapeutics , Interleukins , Interleukin-6 , Inflammation
Brasília; s.n; 25 jul. 2020.
Non-conventional in Portuguese | LILACS, BRISA, PIE | ID: biblio-1117709


O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos e 8 protocolos.

Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Antiviral Agents/therapeutic use , Technology Assessment, Biomedical , Immunoglobulins/therapeutic use , Cross-Sectional Studies , Cohort Studies , Interleukins/antagonists & inhibitors , Adrenal Cortex Hormones/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Leflunomide/therapeutic use , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Neuromuscular Blocking Agents/therapeutic use
Alerta (San Salvador) ; 3(2)30 abril 2020. ilus, tab
Article in Spanish | LILACS | ID: biblio-1095895


No hay tratamiento antiviral específico para el COVID-19. Sin embargo, conocimientos adquiridos durante los brotes del SARS y el MERS, en conjunto con la información obtenida con COVID-19, han permitido detectar varios objetivos terapéuticos en el ciclo de replicación del virus, y en su patogénesis. Se incluye la evidencia actual con respecto a los principales tratamientos propuestos para COVID-19, reutilizados o experimentales, mediante una revisión de la literatura científica a la fecha. Debido a la falta de ensayos controlados aleatorios, se incluyeron: informes de casos, series de casos y artículos de revisión. Globalmente se están llevando a cabo múltiples estudios con el fin de identificar agentes que sean efectivos ante COVID-19, en los siguientes objetivos estratégicos: inhibición de la entrada/fusión del virus (anticuerpos neutralizantes, inhibidores de proteasa de serina transmembrana 2, cloroquina, hidroxicloroquina y umifenovir); interrupción de la replicación viral (remdesivir, favipiravir, lopinavir/ritonavir e ivermectina) y supresión de la respuesta inflamatoria excesiva (corticosteroides, tocilizumab, e inmunoglobulina). Aún no existe un tratamiento efectivo y seguro contra COVID-19; los fármacos descritos en esta revisión se administran como uso compasivo de drogas, o bien, como parte de un ensayo clínico. La terapia de soporte continúa siendo el pilar del manejo de COVID-19.(AU)

There is no specific antiviral treatment for COVID-19. However, knowledge acquired during the SARS and MERS outbreaks, together with the information obtained with COVID-19, have allowed the detection of various therapeutic targets in the virus replication cycle, and in its pathogenesis. The current evidence regarding the leading treatments proposed for COVID-19, reused or experimental, is included through a review of the scientific literature to date. Due to the lack of randomized controlled trials, the following were involved: case reports, case series and review articles. Globally, multiple studies are being carried out in order to identify agents that are effective against COVID-19, upon the following strategic objectives: inhibition of viral entry/fusion (neutralizing antibodies, transmembrane serine protease 2 inhibitors, chloroquine, hydroxychloroquine, and umifenovir); interruption of viral replication (remdesivir, favipiravir, lopinavir/ritonavir and ivermectin), and suppression of excessive inflammatory response (corticosteroids, tocilizumab, and immunoglobulin). There is still no effective and safe treatment against COVID-19; the medications described in this review are given as compassionate drug use, or as part of a clinical trial. Support therapy continues to be COVID-19 management cornerstone.(AU)

Humans , Interleukins/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/therapeutic use , Hydroxychloroquine/therapeutic use , Drug Combinations
Braz. j. otorhinolaryngol. (Impr.) ; 86(1): 23-29, Jan.-Feb. 2020. tab
Article in English | LILACS | ID: biblio-1089369


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.

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
Braz. j. med. biol. res ; 53(1): e8669, Jan. 2020. tab, graf
Article in English | LILACS | ID: biblio-1055478


This study aimed to investigate the therapeutic effect of fasudil on treating experimental autoimmune neuritis (EAN). Twenty-four EAN mice were randomly assigned to fasudil treatment (Fasudil group) or saline treatment (EAN model group) for 28 days. Clinical symptom score was evaluated every other day; inflammatory cell infiltration, demyelination, anti-myelin basic protein (MBP), inflammatory cytokines, inducible nitric oxide synthase (iNOS), and arginase-1 were detected in sciatic nerves at day 28. Th1, Th2, Th17, and Tregs proportions in splenocytes were detected at day 28. Clinical symptom score was found to be attenuated in the Fasudil group compared to the EAN model group from day 12 to day 28. Sciatic nerve inflammatory cell counts by HE staining and demyelination by luxol fast blue staining were both reduced, while MBP was increased in the Fasudil group compared to the EAN model group at day 28. Interferon γ (IFN-γ) and interleukin (IL)-17 were reduced, while IL-4 and IL-10 were elevated in the Fasudil group at day 28. Sciatic nerve M1 macrophages marker iNOS was decreased while M2 macrophages marker arginase-1 was increased in the Fasudil group at day 28. CD4+IFN-γ+ (Th1) and CD4+IL-17+ (Th17) cell proportions were both decreased, CD4+IL-4+ (Th2) cell proportion was similar, while CD25+FOXP3+ (Treg) cell proportion in splenocytes was increased in the Fasudil group. In summary, fasudil presented a good therapeutic effect for treating EAN by attenuating Th1/Th17 cells and promoting Tregs activation as well as M2 macrophages polarization.

Animals , Female , Rabbits , Interleukins/blood , Interferon-gamma/blood , T-Lymphocytes, Helper-Inducer/drug effects , Neuritis, Autoimmune, Experimental/drug therapy , Sciatic Nerve/drug effects , Sciatic Nerve/metabolism , Time Factors , Real-Time Polymerase Chain Reaction , RNA, Mitochondrial , Mice, Inbred C57BL , Neuritis, Autoimmune, Experimental/blood
Braz. j. med. biol. res ; 53(9): e9880, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132558


Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are inflammatory diseases with different bone remodeling patterns. Fibroblast-like synoviocytes (FLS) are cells involved in the transition from an acute and reparable phase to a chronic and persistent stage in these diseases. The distinction of joint phenotypes involves inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and IL-22 directly or through key signaling pathways such as Wnt. To evaluate the role of FLS as the source of Wnt antagonists (sFRP3/FRZB and Dkk1) in the synovia, levels of TNF- α, IL-17, IL-22, Dkk1, and sFRP3 were measured by ELISA directly in the synovial fluid of patients with RA, PsA, or AS. Dkk1 and sFRP3 were also measured in the FLS culture supernatants after different inflammatory stimulus. sFRP3 and Dkk1 are constitutively expressed by FLS. IL-22 and sFRP3 were positively correlated (r=0.76; P<0.01) in synovial fluid. The stimulation of FLS with IL-22, but not TNF-alpha and IL-17, increased the production of sFRP3. No stimulus altered the basal expression of Dkk1. These results showed, for the first time, the ability of IL-22 to increase the expression of sFRP3/FRZB by human FLS in both in vitro and ex vivo models. This finding linked IL-22 to local inhibition of Wnt signaling and possibly to blockade of osteogenesis. Furthermore, FLS presented as a source of this inhibitor in synovial fluid, assigning to this cell a bone injury mechanism.

Humans , Male , Female , Adult , Middle Aged , Interleukins/metabolism , Synoviocytes , Synovial Membrane , Cells, Cultured , Tumor Necrosis Factor-alpha , Fibroblasts
Korean Circulation Journal ; : 250-263, 2020.
Article in English | WPRIM | ID: wpr-811353


BACKGROUND AND OBJECTIVES: To reveal the detail mechanism of miR-484 on myocardial ischemia-reperfusion (MI/R) injury.METHODS: Rats model of MI/R injury was established based on control (Con; sham operate) group, ischemia-reperfusion (I/R) group, miR-484 treatment (miR) group, and I/R-negative control (IR-C) group, followed by pathological and interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β expression evaluation. Then the myocardial apoptosis, as well as the expression of miR-484, caspase-3, and caspase-9 in myocardium were examined. Finally, the regulatory relation between miR-484 and SMAD family member 7 (SMAD7) was predicated, followed by verification analysis.RESULTS: Compared with Con group, the expression of miR-484 in I/R and IR-C group was decreased. Compared with I/R and IR-C group, the expression of miR-484 was increased in miR group. Compared with Con group, the expression levels of IL-6, TNF-α, and IL-1β in cardiac myocytes of I/R group and IR-C group were increased. Compared with Con group, the apoptotic index, membrane potential of I/R, and the expression of caspase-3/9 were increased in IR-C group. Compared with the I/R and IR-C groups, the apoptotic index of myocardial cells in the ischemic region was decreased, the membrane potential was increased, and the expression of caspase-3/9 was decreased significantly in the miR group. SMAD7 was the target gene of miR-484.CONCLUSIONS: MiR-484 protected myocardial cells from I/R injury by suppressing caspase-3 and caspase-9 expression during cardiomyocyte apoptosis. MiR-484 reduced the expression of IL-6, TNF-α, and IL-1β in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells.

Animals , Apoptosis , Caspase 3 , Caspase 9 , Humans , Interleukin-6 , Interleukins , Membrane Potential, Mitochondrial , Membrane Potentials , Myocardium , Myocytes, Cardiac , Rats , Reperfusion Injury , Tumor Necrosis Factor-alpha
Article in English | WPRIM | ID: wpr-811062


PURPOSE: Th17-associated inflammation is increased in chronic rhinosinusitis with nasal polyp (CRSwNP), and is associated with disease severity and steroid resistance. Overexpressed interleukin (IL)-17A affects CRSwNP by tissue remodeling, eosinophilic accumulation, and neutrophilic infiltration. We aimed to identify the role of IL-17A in CRSwNP and to evaluate the effects of anti-IL-17A blocking antibody on nasal polyp (NP) formation using a murine NP model. Moreover, we sought to investigate whether the inhibition of mechanistic target of the rapamycin (mTOR) signal pathway could suppress IL-17A expression and NP formation.METHODS: Human sinonasal tissues from control subjects and patients with chronic rhinosinusitis (CRS) were analyzed using immunohistochemistry (IHC) and immunofluorescence staining. The effects of IL-17A neutralizing antibody and rapamycin were evaluated in a murine NP model. Mouse samples were analyzed using IHC, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay.RESULTS: IL-17A+ inflammatory cells were significantly increased in number in NP from patients with CRSwNP compared to that in uncinate process tissues from control subjects and patients with CRS without NP or CRSwNP. CD68+ M1 macrophages dominantly expressed IL-17A, followed by neutrophils and T helper cells, in NP tissues. Neutralization of IL-17A effectively reduced the number of NPs, inflammatory cytokines, and IL-17A-producing cells, including M1 macrophages. Inhibition of IL-17A via the mTOR pathway using rapamycin also attenuated NP formation and inflammation in the murine NP model.CONCLUSIONS: IL-17A possibly plays a role in the pathogenesis of CRSwNP, the major cellular source being M1 macrophage in NP tissues. Targeting IL-17A directly or indirectly may be an effective therapeutic strategy for CRSwNP.

Animals , Antibodies, Neutralizing , Cytokines , Enzyme-Linked Immunosorbent Assay , Eosinophils , Fluorescent Antibody Technique , Humans , Immunohistochemistry , Inflammation , Interleukin-17 , Interleukins , Macrophages , Mice , Nasal Polyps , Neutrophils , Real-Time Polymerase Chain Reaction , Signal Transduction , Sinusitis , Sirolimus , T-Lymphocytes, Helper-Inducer
Article in English | WPRIM | ID: wpr-810960


BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.

Amniocentesis , Amniotic Fluid , Area Under Curve , Biomarkers , Blood Proteins , Cervix Uteri , Complement System Proteins , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-6 , Interleukins , Labor Stage, First , Outcome Assessment, Health Care , Plasma , Pregnancy , Progesterone , Retrospective Studies , Risk Factors , Tissue Inhibitor of Metalloproteinase-1 , Tissue Inhibitor of Metalloproteinases
Article in English | WPRIM | ID: wpr-810950


BACKGROUND: Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.METHODS: RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.RESULTS: Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.CONCLUSION: RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

Arthritis, Rheumatoid , Cholecalciferol , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Follow-Up Studies , Hand , Humans , In Vitro Techniques , Interleukin-17 , Interleukin-6 , Interleukins , Osteoclasts , Retrospective Studies , Vitamin D , Vitamins , Wrist
Article in English | WPRIM | ID: wpr-786141


OBJECTIVE: The microRNA (miR)-10b is the T helper (Th) 17 cell specific in patients with ankylosing spondylitis (AS). The interleukin (IL)-22, which is closely related to Th17 cells, has been implicated in the regulation of new bone formation in experimental models. Therefore, the aim of this study was to evaluate whether miR-10b affects bone formation via the IL-22 pathway in AS.METHODS: Primary CD4+ T cells from AS were purified and transfected with miR-10b, anti-miR-10b, or scramble. Cell-surface markers and cytokine expression were analyzed by flow cytometry and enzyme-linked immunosorbent assay. Primary bone-derived cells (BdCs) from the facet joints of the spine were isolated, then osteogenic differentiation of primary BdCs was performed. We assessed alkaline phosphatase (ALP) activity and staining of BdCs at early time points. Alizarin red S staining of BdCs was performed at late time points.RESULTS: Overexpression of miR-10b reduced both IL-22 producing cell frequencies and cytokine production in T cells from the patients with AS. The IL-22 significantly increased ALP staining and bone mineralization. The ALP promotor activity of AS-BdCs was notably higher for the IL-22 concentration. The supernatants of the miR-10b overexpression group suppressed ALP activity on osteogenic progenitor cells from the facet joints of the spine in patients with AS.CONCLUSION: Our data suggest that miR-10b suppresses IL-22 production, which was involved in osteogenic proliferation in AS. Therefore, miR-10b might be a potential therapeutic candidate for regulation of new bone formation in patients with AS.

Alkaline Phosphatase , Calcification, Physiologic , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Interleukins , MicroRNAs , Models, Theoretical , Osteogenesis , Spine , Spondylitis, Ankylosing , Stem Cells , T-Lymphocytes , Th17 Cells , Zygapophyseal Joint
Article in English | WPRIM | ID: wpr-785339


PURPOSE: Osteitis refers to the development of new bone formation and remodeling of bone in chronic rhinosinusitis (CRS) patients; it is typically associated with eosinophilia, nasal polyps (NPs), and recalcitrant CRS. However, the roles of ossification in CRS with or without NPs remain unclear due to the lack of appropriate animal models. Thus, it is necessary to have a suitable animal model for greater advances in the understanding of CRS pathogenesis.METHODS: BALB/c mice were administered ovalbumin (OVA) and staphylococcal enterotoxin B (SEB). The numbers of osteoclasts and osteoblasts and bony changes were assessed. Micro computed tomography (micro-CT) scans were conducted to measure bone thickness. Immunofluorescence, immunohistochemistry, and quantitative polymerase chain reaction were performed to evaluate runt-related transcription factor 2 (RUNX2), osteonectin, interleukin (IL)-13, and RUNX2 downstream gene expression. Gene set enrichment analysis was performed in mucosal tissues from control and CRS patients. The effect of resveratrol was evaluated in terms of osteogenesis in a murine eosinophilic CRS NP model.RESULTS: The histopathologic changes showed markedly thickened bones with significant increase in osteoblast numbers in OVA/SEB-treated mice compared to the phosphate-buffered saline-treated mice. The structural changes in bone on micro-CT were consistent with the histopathological features. The expression of RUNX2 and IL-13 was increased by the administration of OVA/SEB and showed a positive correlation. RUNX2 expression mainly co-localized with osteoblasts. Bioinformatic analysis using human CRS transcriptome revealed that IL-13-induced bony changes via RUNX2. Treatment with resveratrol, a candidate drug against osteitis, diminished the expression of IL-13 and RUNX2, and the number of osteoblasts in OVA/SEB-treated mice.CONCLUSIONS: In the present study, we found the histopathological and radiographic evidence of osteogenesis using a previously established murine eosinophilic CRS NP model. This animal model could provide new insights into the pathophysiology of neo-osteogenesis and provide a basis for developing new therapeutics.

Animals , Computational Biology , Core Binding Factor Alpha 1 Subunit , Enterotoxins , Eosinophilia , Eosinophils , Fluorescent Antibody Technique , Gene Expression , Humans , Immunohistochemistry , Interleukin-13 , Interleukins , Mice , Models, Animal , Mucous Membrane , Nasal Polyps , Nose , Osteitis , Osteoblasts , Osteoclasts , Osteogenesis , Osteonectin , Ovalbumin , Polymerase Chain Reaction , Sinusitis , Transcription Factors , Transcriptome
Article in English | WPRIM | ID: wpr-762184


PURPOSE: Various immune cells, including eosinophils and neutrophils, are known to contribute to the development of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the current understanding of the role of neutrophils in the development of CRSwNP still remains unclear. Therefore, we investigated risk factors for refractoriness of CRSwNP in an Asian population. METHODS: Protein levels of 17 neutrophil-related mediators in nasal polyps (NPs) were determined by multiplex immunoassay, and exploratory factor analysis using principal component analysis was performed. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE) or myeloperoxidase (MPO)-positive cells. Tissue eosinophilic nasal polyp (ENP) and tissue neutrophilia (Neu(high)) were defined as greater than 70 eosinophils and 20 HNE-positive cells, otherwise was classified into non-eosinophilic nasal polyp (NENP) and absence of tissue neutrophilia (Neu(low)). RESULTS: In terms of disease control status, NENP-Neu(low) patients showed the higher rate of disease control than NENP-Neu(high) and ENP-Neu(high) patients. Linear by linear association demonstrated the trend in refractoriness from NENP-Neu(low) to NENP-Neu(high) or ENP-Neu(low) to ENP-Neu(high). When multiple logistic regression was performed, tissue neutrophilia (hazard ratio, 4.38; 95% confidence interval, 1.76-10.85) was found as the strongest risk factor for CRSwNP refractoriness. Additionally, exploratory factor analysis revealed that interleukin (IL)-18, interferon-γ, IL-1Ra, tumor necrosis factor-α, oncostatin M, and MPO were associated with good disease control status, whereas IL-36α and IL-1α were associated with refractory disease control status. In subgroup analysis, HNE-positive cells and IL-36α were significantly upregulated in the refractory group (P = 0.0132 and P = 0.0395, respectively), whereas MPO and IL-18 showed higher expression in the controlled group (P = 0.0002 and P = 0.0009, respectively). Moreover, immunofluorescence analysis revealed that IL-36R⁺HNE⁺-double positive cells were significantly increased in the refractory group compared to the control group. We also found that the ratio of HNE-positive cells to α1 anti-trypsin was increased in the refractory group. CONCLUSIONS: Tissue neutrophilia had an influence on treatment outcomes in the Asian CRSwNP patients. HNE-positive cells and IL-36α may be biomarkers for predicting refractoriness in Asians with CRSwNP. Additionally, imbalances in HNE and α1 anti-trypsin may be associated with pathophysiology of neutrophilic chronic rhinosinusitis.

Asian Continental Ancestry Group , Biomarkers , Eosinophils , Fluorescent Antibody Technique , Humans , Immunoassay , Interleukin 1 Receptor Antagonist Protein , Interleukin-18 , Interleukins , Leukocyte Elastase , Logistic Models , Nasal Polyps , Necrosis , Neutrophils , Oncostatin M , Peroxidase , Principal Component Analysis , Rhinitis , Risk Factors , Sinusitis
Article in English | WPRIM | ID: wpr-762177


PURPOSE: Alterations in the intestinal microbiota in early life affects the development of atopic dermatitis (AD) in humans. This study aimed to further investigate the effects of gut dysbiosis in early life in an ovalbumin (OVA)-induced mouse model of AD. METHODS: The AD mouse model was developed by serial OVA sensitization and mice were treated with an antibiotic cocktail in their drinking water for 2 weeks before primary sensitization. Probiotics (Lactobacillus rhamnosus, 1 × 10⁹ CFU) or 100 µL of fresh fecal supernatant were orally administered daily from 1 week before the first sensitization until the end of the study. RESULTS: The AD mice which received antibiotics had significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. Total systemic immunoglobulin E production and skin interleukin (IL) 4 levels were significantly increased in the antibiotic-treated mice compared to the other groups. Antibiotic treatment also increased the levels of IL17 and group 3 innate lymphoid cells (ILC3) in the gut and significantly suppressed the production of short-chain fatty acids (SCFAs) and decreased the number FOXP3⁺ cells. CONCLUSIONS: Our results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4⁺IL17⁺/CD4⁺FOXP3⁺ regulatory T cells and ILC3s.

Animals , Anti-Bacterial Agents , Cytokines , Dermatitis, Atopic , Drinking Water , Dysbiosis , Fatty Acids , Fatty Acids, Volatile , Feces , Gastrointestinal Microbiome , Humans , Immunoglobulin E , Immunoglobulins , Interleukins , Intestines , Lymphocytes , Mice , Microbiota , Ovalbumin , Ovum , Phenotype , Probiotics , Skin , T-Lymphocytes, Regulatory , Water