Associação entre eventos estressores e citocinas inflamatórias e anti-inflamatórias em pessoas idosas longevas / Association between stressor events and inflammatory and anti-inflammatory cytokines in long-lived older people

Resumo Objetivo investigar a associação entre a frequência de eventos estressores e citocinas em pessoas idosas longevas. Métodos os participantes responderam a um questionário constituído de variáveis sociodemográficas, indicaram quais eventos estressores constantes no Inventário de Eventos Estressores de vida ocorreram nos últimos cinco anos e responderam a escala de depressão geriátrica (GDS). Foram dosados por citometria de fluxo: interleucina (IL) 10, IL-6, IL-4, IL-2, fator de necrose tumoral (TNF-α) e interferon gama (IFN-γ). A análise descritiva foi realizada para a caracterização da amostra. Para investigar a associação entre as variáveis foi desenvolvido um modelo de regressão linear múltipla, utilizando o método Backward. Resultados Participaram da pesquisa 91 pessoas idosas com média de idade de 82 anos. Mais da metade da amostra relatou morte de ente querido como o evento estressor mais prevalente (61%). Nessa amostra foi possível perceber que quanto mais eventos estressores foram relatados, menor o nível de IL-4 (p=0,046), da mesma forma que o estado civil viuvez, onde os dados mostraram que quem é viúvo tem menos eventos estressores em comparação a quem é casado (p=0,037). Conclusão Evidenciou-se a importância de um olhar mais cuidadoso dos profissionais de saúde na avaliação multidimensional da pessoa idosa, de forma que se obtenham subsídios para a implementação de programas e intervenções específicos que possam amenizar a percepção dos eventos estressores vivenciados, colaborando com menores danos decorrentes da imunossenescência.

Abstract Objective To investigate the association between the frequency of stressor events and cytokines in long-lived older people. Methods The participants answered a questionnaire consisting of sociodemographic variables, indicated which stressor events included in the Stressor Life Events Inventory occurred in the last five years and answered the Geriatric Depression Scale (GDS). The following were measured by flow cytometry: interleukin (IL) 10, IL-6, IL-4, IL-2, tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ). We carried out a descriptive statistical analysis in order to characterize the sample. To investigate the association between the variables, a multiple linear regression model was developed, using the Backward method. Results 91 older people with an age average of 82 years participated in the research. More than half of the sample reported the death of a loved one as the most prevalent stressor event (61%). In this sample, it was possible to notice that the more stressor events were reported, the lower the level of IL-4 (p=0.046), as well as the marital status of widowhood, where data showed that those who are widowed have fewer stressor events in comparison to who is married (p=0.037). Conclusion The importance of a more careful look by health professionals in older people multidimensional assessment was evidenced, so that subsidies are obtained for the implementation of specific programs and interventions that can ease the perception of the stressor events experienced, collaborating with less resulting damage of immunosenescence.

Effect of fasudil on experimental autoimmune neuritis and its mechanisms of action

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.

The effect of exercise on interferon gamma, body fat and bmi of kidney transplant patients / Efeito do exercício sobre interferon gama, gordura corporal e imc em pacientes com transplante renal / Efecto del ejercicio sobre el interferón gamma y el imc de los pacientes con trasplante de riñón

INTRODUCTION: Poor physical function and obesity are well documented in kidney transplant patients. Significant health benefits result from regular physical activity, many of which are important for kidney transplant patients. OBJECTIVE: The aim of this study was to investigate the effects of 10-week combined exercises on Interferon Gamma (IFNγ), body fat percentage (BF%) and body mass index (BMI) in kidney transplant patients. METHOD: In a randomized controlled experimental design, 44 kidney transplant patients aged 20-50 years were randomly divided into two groups of exercise (n=23) and control (n=21). The exercise group participated in a cumulative training program for 10 weeks, three days a week, 60­90 minutes per day at 40-65% of predicted maximal heart rate reserve. A 5 ml venous blood sample and anthropometric parameters were taken from the subjects at baseline and after 10 weeks. RESULTS: The exercise group showed an improvement in BF% (from 31.80±5.64 to 28.86 ± 5.82, p =0.001) and BMI (from 26.23 ± 1.81 to 25.45 ± 2.11, p = 0.001), but there was no significant change in the IFNγ level (from 0.06 ± 0.02 to 0.06 ± 0.02, p = 0.829). There was a significant difference between the control and exercise groups for BF% (p = 0.001) and BMI (p = 0.001). CONCLUSION: As a take-home message, it should be mentioned that combined exercise intervention is inexpensive and portable and can be performed at home or health centers for kidney transplant patients to reduce their weight and BF%. Evidence Level I; High quality randomized trial with or without statistically significant difference, but with narrow confidence intervals.

INTRODUÇÃO: A função física deficiente e a obesidade são bem documentadas em pacientes com transplante renal. A atividade física regular resulta em benefícios significativos para a saúde, muitos dos quais são importantes para os pacientes com transplante de rim. OBJETIVO: O objetivo deste estudo foi investigar os efeitos de 10 semanas de exercícios combinados sobre interferon gama (IFN-γ), percentual de gordura corporal (GC) e índice de massa corporal (IMC) nesses pacientes. MÉTODOS: Em um estudo randomizado experimental controlado, 44 pacientes com transplante renal com idade entre 20 e 50 anos foram divididos em um grupo exercício (n = 23) e um grupo controle (n = 21). O grupo exercício participou em um programa de treinamento cumulativo por 10 semanas, três dias por semana, 60 a 90 minutos por dia, com 40% a 65% da frequência cardíaca de reserva prevista. Foram coletadas amostras de sangue venoso de 5 ml, assim como os parâmetros antropométricos dos indivíduos no início do programa e depois de 10 semanas. RESULTADOS: O grupo exercício apresentou melhora do percentual de GC (31,80 ± 5,64 para 28,86 ± 5,82, p = 0,001) e do IMC (26,23 ± 1,81 para 25,45 ± 2,11, p = 0,001), mas não houve mudança significativa no nível de IFN-γ (0,06 ± 0,02 para 0,06 ± 0,02, p = 0,829). Houve diferença significativa entre os grupos controle e exercício no percentual de GC (p = 0,001) e no IMC (p = 0,001). CONCLUSÃO: A mensagem a ser lembrada é que a intervenção com exercícios combinados é de baixo custo e os aparelhos necessários são portáteis, e pode ser realizada em casa ou em centros de saúde pelos pacientes de transplante renal, visando reduzir o peso e o percentual de GC. Nível de Evidência I; Estudo clínico randomizado de alta qualidade com ou sem diferença estatisticamente significante, mas com intervalos de confiança estreitos.

INTRODUCCIÓN: el bajo funcionamiento físico y la obesidad están bien documentados en pacientes con trasplante de riñón. Los beneficios significativos para la salud son el resultado de la actividad física regular, muchos de los cuales son importantes para los pacientes con trasplante de riñón. OBJETIVO: El objetivo de este estudio fue investigar los efectos de los ejercicios combinados de 10 semanas sobre Interferón-Gamma (IFNγ), porcentaje de grasa corporal (% BF) e índice de masa corporal (IMC) en pacientes con trasplante renal. MÉTODO: en un diseño experimental controlado aleatorio, 44 pacientes con trasplante renal, de 20-50 años, se dividieron aleatoriamente en dos grupos de ejercicio (n = 23) y control (n = 21). El grupo de ejercicio participó en un programa de entrenamiento acumulativo durante 10 semanas, tres días a la semana, 60 a 90 minutos por dia, com 40 a 65% de la reserva máxima prevista para frecuencia cardiaca. Se tomaron 5 ml de muestra de sangre de Venus y parámetros antropométricos de los sujetos en la línea de base al inicio y luego de 10 semanas. RESULTADOS: El grupo de ejercicio mostró una mejora en el porcentaje de BF (de 31,80 ± 5,64 a 28,86 ± 5,82, p = 0,001) y el IMC (de 26,23 ± 1,81 a 25,45 ± 2,11, p = 0,001), pero no hubo un cambio significativo en el nivel de IFNγ (de 0.06 ± 0.02 a 0.06 ± 0.02, p = 0.829). Hubo una diferencia significativa entre el control y los grupos de ejercicio para BF% (p = 0.001) e IMC (p = 0.001). CONCLUSIÓN: como mensaje de inicio se debe mencionar que la intervención combinada con ejercicios es económica y portátil, y puede realizarse en el hogar o en centros de salud para que los pacientes con trasplante de riñón disminuyan su peso y BF%. Nivel de Evidencia I; Estudio clínico aleatorio de alta calidad, con o sin diferencia estadísticamente significativa, pero con intervalos de confianza estrechos.

Histopathologic aspects of experimental cysticercosis and in situ cytokines profile in C57BL/6 mice / Aspectos histopatológicos da cisticercose experimental e perfil de citocinas in situ em camundongos C57BL/6

ABSTRACT Neurocysticercosis (NCC) is one of the parasitic infections that most affects the central nervous system. The knowledge regarding its immunopathogenesis and pathophysiology needs broadening. Taenia crassiceps cysticerci are used as the NCC experimental model. The aim of this work was to describe the general pathological processes and the in situ cytokine profile in C57BL/6 mice inoculated intracranially with viable T. crassiceps cysticerci. The histopathology analysis showed cysticerci in the extraparenchymal and intraventricular region, mononuclear inflammatory infiltration surrounding the parasite, microgliosis and meningitis. The analysis of the in situ immune profiles showed a predominance of the Th2 response. The IL-4 and IL-10 dosages were significantly increased in the infected group. The decrease in the INF-gamma dosage reflects the immunomodulation from the cysticerci. In conclusion, a T. crassiceps NCC infection in C57BL/6 mice triggers an inflammatory response, a predominance of Th2 type in situ profile, with mononuclear inflammatory cell infiltration, meningitis and microgliosis.

RESUMO Neurocisticercose (NCC) é uma das doenças parasitárias que mais afeta o sistema nervoso central. É necessário aprofundar o conhecimento em relação à sua imunopatogênese e patofisiologia. Os cisticercos de Taenia crassiceps são utilizados como modelo experimental para estudos da NCC. O objetivo deste trabalho foi descrever os processos patológicos gerais e o perfil de citocinas in situ em camundongos C57BL/6 inoculados via intracerebral com cisticercos viáveis de T. crassiceps. A análise histopatológica demonstrou cisticercos nas regiões extra-parenquimatosa e intraventricular, infiltrado inflamatório de células mononucleares ao redor do parasita, microgliose e meningite. A análise in situ do perfil de citocinas mostrou uma predominância da resposta Th2. As dosagens de IL-4 e IL-10 foram significativamente maiores no grupo infectado. Conclui-se que a NCC por T. crassiceps em camundongos C57BL/6 induz uma resposta inflamatória com predominância in situ de citocinas do perfil Th2, com infiltrado inflamatório de células mononucleares, meningite e microgliose.

Social conditions and immune response in human immunodeficiency virus-seropositive pregnant women: a cross-sectional study in Brazil

Abstract INTRODUCTION The functioning of the immune system during pregnancy is altered in both human immunodeficiency virus (HIV)-infected and uninfected women. Unfavorable socioeconomic conditions have been indicative of higher morbidity and mortality and worsening of the immune system. The aim of this study was to correlate social status with levels of interleukin (IL)-10 (non-inflammatory) and interferon-gamma (IFN-γ; inflammatory) cytokines. METHODS A cross-sectional study was conducted with three groups of women: 33 pregnant HIV-infected (G1); 40 non-pregnant, HIV-infected (G2); and 35 pregnant, HIV-uninfected. To measure the social status, a compound indicator called the social status index (SSI), was established using sociodemographic variables (i.e., education level, housing conditions, per capita income, and habitation and sanitary conditions). RESULTS The HIV-infected women had a higher proportion of unfavorable SSI (73% and 75% of G1 and G2, respectively). There were significantly lower IL-10 levels in the G1 group with both unfavorable and favorable SSI than in the other groups. No significant difference in IFN-γ levels was observed among groups. However, the G1 group had higher IFN-γ values among both favorable and unfavorable SSI groups. CONCLUSIONS Higher rates of unfavorable conditions, including lower education levels, IL-10 levels, and a trend for higher IFN-γ levels, were identified among HIV-infected women, pregnant and non-pregnant. These factors may interfere in health care and lead to poor outcomes during pregnancy. Therefore, we suggest that health policies could be created to specifically address these factors in this population.

Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease

ABSTRACT Periodontal disease has been associated with elevations of blood cytokines involved in atherosclerosis in systemically healthy individuals, but little is known about this association in stable cardiovascular patients. The aim of this study was to assess the association between periodontal disease (exposure) and blood cytokine levels (outcomes) in a target population of patients with stable coronary artery disease (CAD). Material and Methods This cross-sectional study included 91 patients with stable CAD who had been under optimized cardiovascular care. Blood levels of IL-1β, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by Luminex technology. A full-mouth periodontal examination was conducted to record probing depth (PD) and clinical attachment (CA) loss. Multiple linear regression models, adjusting for gender, body mass index, oral hypoglycemic drugs, smoking, and occurre:nce of acute myocardial infarction were applied. Results CAD patients that experienced major events had higher concentrations of IFN-γ (median: 5.05 pg/mL vs. 3.01 pg/mL; p=0.01), IL-10 (median: 2.33 pg/mL vs. 1.01 pg/mL; p=0.03), and TNF-α (median: 9.17 pg/mL vs. 7.47 pg/mL; p=0.02). Higher numbers of teeth with at least 6 mm of CA loss (R2=0.07) and PD (R2=0.06) were significantly associated with higher IFN-γ log concentrations. Mean CA loss (R2=0.05) and PD (R2=0.06) were significantly related to IL-10 concentrations. Elevated concentrations of TNF-α were associated with higher mean CA loss (R2=0.07). Conclusion Periodontal disease is associated with increased systemic inflammation in stable cardiovascular patients. These findings provide additional evidence supporting the idea that periodontal disease can be a prognostic factor in cardiovascular patients.

Primary dengue virus infections induce differential cytokine production in Mexican patients

Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.

Vitamin A supplementation reduces the Th17-Treg – Related cytokines in obese and non-obese women

ABSTRACT Objective The objective of the present study was to investigate the effect of vitamin A supplementation on serum Th17 (IL-6, IL-17, IFNγ) and Treg (TGF-β, IL-10) related cytokines in obese and non-obese women. Subjects and methods In a randomized double blind placebo controlled design, 56 obese women were randomly assigned to receive either an oral dose of 25,000 IU retinyl palmitate or placebo per day for 4 months. Twenty eight ages matched non-obese women were also received vitamin A. At the study entry, anthropometric variables were measured and serum Th17 and Treg related cytokine profile were determined at baseline and 4 months after intervention. Results Significantly higher baseline concentrations of IL-6 were observed in obese compared with non-obese women (P < 0.05). However, the initial concentrations of other cytokines were not significantly different between groups. The mean concentrations of IL-17 and TGF-β were significantly decreased after vitamin A supplementation in non-obese and obese women respectively. Positive relationships between IL-17 and IL-10 (r = 0.42, P < 0.001), TGF-β and IL-17 (r = 0.35, P < 0.001) and between IL-10 and IFN-γ (r = 0.41, P = 0.002) in total participants were also observed. Conclusions The results of the present study showed for the first time that vitamin A supplementation reduces serum concentrations of IL-17 and TGF-β in reproductive age women. Further studies are needed to explore the possible underlying mechanisms.

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Evaluation of systemic inflammatory responses in cholecystectomy by means of access. Single-port umbilical incision, transvaginal NOTES, laparoscopy and laparotomy

PURPOSE: To evaluate and compare clinical and inflammatory responses to the surgical trauma caused by cholecystectomy via several access approaches: single-port umbilical incision (SILS), transvaginal natural orifice transluminal endoscopic surgery (NOTES), laparoscopy, and Laparotomy.METHODS: Twenty-eight female pigs were equally divided into four groups and submitted to cholecystectomy by single-port umbilical incision, transvaginal NOTES, laparoscopy, or Laparotomy. An additional five animals served as controls (sham group). Animals were monitored perioperatively regarding anesthesia and surgical procedure times, as well as for the presence of complications. Postoperatively, they were evaluated regarding time to ambulation and feeding, and the presence of clinical events. Procalcitonin, C-reactive protein (CRP), and AQUI feron-gamma (IFN-γ) measurements were performed before surgery and immediately, two days, and seven days after surgery. Animals were sacrificed and necropsied at seven days after surgery.RESULTS: All procedures were successfully performed as proposed in each group. Only minor complications, such as gallbladder perforation and bleeding from the liver bed, were observed during surgery in all groups. The vaginal NOTES group showed higher anesthesia and surgical procedure times compared to the other groups (p<0.001). No other between-group differences in perioperative or postoperative times, clinical evolution, or serum inflammatory markers were observed. Only adhesions were found on necropsy, with no differences between groups.CONCLUSION: The single-port umbilical and transvaginal NOTES access approaches were feasible and safe compared to laparoscopic and laparotomy for cholecystectomy.

Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

Serum Levels of Interferon Gamma in Patients with Brucellosis in a Saudi Hospital.

Background: Brucellosis is a major zoonotic disease that is endemic in Saudi Arabia and it remains a major health problem that has not been eradicated in the country yet. Place and Duration of Study: This retrospective study was conducted in a Saudi Hospital at Al Madinah city during the period of 1 November, 2010 to 31 October, 2011. Methodology: All sera of patients suspected to have brucellosis (n= 65) and 18 healthy subjects were tested for brucella antibody using slide latex agglutination (SAT) and ELISA. Quantitation of IFN-ɣ was also done using ELISA. Results: Brucellosis was detected in all age groups but the incidence was higher and reached 33.3% in age group (40- <50) years with average of 43.9±2.53 years. Male to female ratio in infected patients was 2:1 by using SAT. The incidence of seropositive cases was high (80.1%) in the three months (April, May and June), with the highest peak in May (46.7%). Drinking raw milk was the most encountered risk factor with a prevalence of 66.1% followed by consumption of milk products (11.9%). The most prevalent species among the examined cases was B. melitensis (93.3%). Among the studied cases, 60 cases (92.3%) were serologically positive for brucellosis by SAT. Among the 60 cases yielding significant titers against brucella, 14 sera (23.3%) had agglutinin levels of 1:80, 34 sera (56.7%) had titers of 1:160 and 12 sera (20%) had titers of 1:320. By estimating IgM and IgG levels in the sera of examined cases using ELISA, 52 cases (80%) had brucellaIgM while 42 cases (64.6%) had brucella IgG. Sensitivities of SAT, IgM ELISA and IgG ELISA were 91.5%, 88.1% and 71.2%, respectively compared with combined ELISA. Mean IFN-ɣ levels ± SD in the subacute phase was 136.7±70.07pg/ml, 120.2±54.25pg/ml in the acute phase, and 121.3±51.09 pg/ml in the chronic phase of brucellosis. Conclusion: The sensitivity and specificity of ELISA to diagnose human brucellosis was higher when combined ELISA (IgM/IgG or both) was used. Mean IFN-ɣ levels were lower, but not significantly, in the chronic phase of the disease than in the sub acute phase and healthy subjects.

[Diazinon alters sex hormones, Interferon-gamma, Interleukin-4 and 10 in male Wistar rats]

Agricultural toxins including organochlorine and organophosphorus families cause damages in the various tissues in humans. Diazinon is a non-systemic organophosphate insecticide. This study was carried out to determine the effect of Diazinon on sex hormone, interferon gamma, interleukin-4 and 10 in male rats. In this experimental study 24 adult male Wistar rats were randomly allocated into four groups. Three experimental groups were received Diazinon 5 days per week for one month at 0.3, 3 and 30 mg/kg/bw intraperitoneally, while controls received nothing. Seven days after the last injection, blood samples were obtained and the serum testosterone, FSH, LH, interferon gamma, interleukin-4 and interleukin-10 were measured. Serum level of Interleukin-10 significantly increased in experimental group [30 mg/kg/bw of Diazinon] compared to controls [P<0.05]. Serum level of Interleukin-10 significantly decreased in 0.3 mg/kg/bw and 3mg/kg/bw of Diazinon groups compared to controls [P<0.05]. Interleukin-4 level was only significant in the group receiving 30 mg/kg/bw of Diazinon [P<0.05]. Reduction in interferongamma level was not significant between control and experimental groups. FSH significantly reduced in the three experimental groups in comparison with controls [P<0.05]. Testosterone level was significantly increased in experimental groups compared to control [P<0.05]. Diazinon increases interleukin-10 and testosterone and reduces FSH hormone in the rat

Follow-up Testing of Interferon-Gamma Release Assays Are Useful in Ankylosing Spondylitis Patients Receiving Anti-Tumor Necrosis Factor Alpha for Latent Tuberculosis Infection

We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFalpha and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFalpha, including type and treatment duration. The median duration of anti-TNFalpha was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFalpha in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFalpha.

Induction of antibody and interferon-gamma production in mice immunized with virus-like particles of swine hepatitis E virus

Virus-like particles (VLPs) composed of the truncated capsid protein of swine hepatitis E virus (HEV) were developed and immune responses of mice immunized with the VLPs were evaluated. IgG titers specific for the capsid protein of swine HEV were significantly higher for all groups of mice immunized with the VLPs than those of the negative control mice. Splenocytes from mice immunized with the VLPs also produced significantly greater quantities of interferon (IFN)-gamma than interleukin (IL)-4 and IL-10. These newly developed swine HEV VLPs have the capacity to induce antigen-specific antibody and IFN-gamma production in immunized mice.

Kinetics of T-cell-based assays on cerebrospinal fluid and peripheral blood mononuclear cells in patients with tuberculous meningitis

BACKGROUND/AIMS: The goal of this study was to monitor tuberculosis (TB)-specific T-cell responses in cerebrospinal fluid-mononuclear cells (CSF-MCs) and peripheral blood mononuclear cells (PBMCs) in patients with tuberculous meningitis (TBM) over the course of anti-TB therapy. METHODS: Adult patients (> or = 16 years) with TBM admitted to Asan Medical Center, Seoul, South Korea, were prospectively enrolled between April 2008 and April 2011. Serial blood or CSF samples were collected over the course of the anti-TB therapy, and analyzed using an enzyme-linked immunosorbent spot (ELISPOT) assay. RESULTS: Serial ELISPOT assays were performed on PBMCs from 17 patients (seven definite, four probable, and six possible TBM) and CSF-MC from nine patients (all definite TBM). The median number of interferon-gamma (IFN-gamma)-producing T-cells steadily increased during the first 6 months after commencement of anti-TB therapy in PBMCs. Serial CSF-MC ELISPOT assays revealed significant variability in immune responses during the first 6 weeks of anti-TB therapy, though early increases in CSF-MC ELISPOT results were associated with treatment failure or paradoxical response. CONCLUSIONS: Serial analysis of PBMCs by ELISPOT during the course of treatment was ineffective for predicting clinical response. However, increases in TB-specific IFN-gamma-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure.

Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis / Marcadores inflamatorios e imunogeneticos e sua relacao com tuberculose pulmonar

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis. METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts. RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels. CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment. .

OBJETIVO: Descrever os níveis séricos das citocinas IL-10, TNF-α e IFN-γ, assim como polimorfismos presentes em genes envolvidos na sua transcrição, e sua associação com marcadores de resposta inflamatória aguda em pacientes com tuberculose. MÉTODOS: Estudo descritivo e longitudinal realizado em 81 pacientes com tuberculose pulmonar atendidos em dois hospitais de referência. Foram coletadas informações sociodemográficas, conversão bacteriológica na oitava semana de tratamento antituberculose, polimorfismos relacionados às citocinas estudadas, níveis séricos dessas citocinas, assim como de proteína C reativa (PCR). Também foram avaliados VHS e contagem de CD4+. RESULTADOS: A mediana de idade dos pacientes era de 43 anos, sendo 67 (82,7%) do sexo masculino e 8 (9,9%) infectados por HIV. Os pacientes com níveis elevados de IFN-γ e baixos níveis de IL-10 apresentaram valores mais elevados de VHS. Não houve associação dos polimorfismos do gene IFN-γ na posição +874 e do gene TNF-α na posição −238 com os níveis das citocinas correspondentes. Houve uma associação entre polimorfismos do gene IL-10 nas posições −592 e −819 (mas não −1082) e baixos níveis de IL-10. Houve uma associação negativa entre a taxa de conversão bacteriológica na oitava semana de tratamento e níveis de PCR. CONCLUSÕES: Nossos resultados sugerem que marcadores genéticos e de resposta inflamatória aguda podem ser úteis na predição da resposta ao tratamento antituberculose. .

Severe visceral leishmaniasis in children: the relationship between cytokine patterns and clinical features

Introduction The relationship between severe clinical manifestations of visceral leishmaniasis (VL) and immune response profiles has not yet been clarified, despite numerous studies on the subject. This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, particularly, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil). Methods We conducted a prospective, descriptive study between May 2008 and December 2009. This study was based on an assessment of all pediatric patients with VL who were observed in a reference hospital in Maranhão. Results Among 27 children, 55.5% presented with more than one sign of severity or warning sign. Patients without signs of severity or warning signs and patients with only one warning sign had the highest interferon-gamma (IFN-γ) levels, although their interleukin 10 (IL-10) levels were also elevated. In contrast, patients with the features of severe disease had the lowest IFN-γ levels. Three patients who presented with more than two signs of severe disease died; these patients had undetectable interleukin 2 (IL-2) and IFN-γ levels and low IL-10 levels, which varied between 0 and 36.8pg/mL. Conclusions Our results showed that disease severity was associated with low IFN-γ levels and elevated IL-10 levels. However, further studies with larger samples are needed to better characterize the relationship between disease severity and cytokine levels, with the aim of identifying immunological markers of active-disease severity. .

The influence of leptin on Th1/Th2 balance in obese children with asthma / Influência da leptina no equilíbrio Th1/Th2 em crianças asmáticas obesas

OBJECTIVE: In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. METHODS: We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. RESULTS: Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted) than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group. CONCLUSIONS: Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity. .

OBJETIVO: A obesidade induz a produção de leptina em asmáticos e está associada à gravidade da doença. Nosso objetivo foi avaliar os níveis de leptina sérica e seu efeito no equilíbrio Th1/Th2 em crianças asmáticas obesas e não obesas e investigar a associação desses níveis com desfechos clínicos. MÉTODOS: O estudo envolveu 50 crianças atópicas com diagnóstico médico de asma persistente moderada a grave e 20 controles. Os asmáticos foram agrupados como obesos (n = 25) e não obesos (n = 25) de acordo com o percentil do índice de massa corpórea. Amostras de sangue periférico foram coletadas de todos os sujeitos, e os níveis de leptina, IFN-γ e IL-4 foram determinados. A gravidade da asma foi avaliada por um escore de sintomas de asma, e os resultados foram correlacionados com os parâmetros estudados. RESULTADOS: Os níveis séricos de leptina foram significativamente maiores nos asmáticos obesos do que nos asmáticos não obesos, assim como nos asmáticos comparados aos controles, enquanto os níveis de IFN-γ foram significativamente maiores e os de IL-4 foram significativamente menores nos asmáticos obesos do que nos asmáticos não obesos. Os asmáticos obesos tiveram maiores escores de sintomas de asma e VEF1 (% do previsto) significativamente menor que os asmáticos não obesos. Houve uma correlação positiva significativa entre os níveis de leptina e IFN-γ somente entre os asmáticos obesos. CONCLUSÕES: Embora a leptina esteja envolvida na patogênese da asma em crianças asmáticas obesas ou não, seu efeito é maior naquelas obesas. Na presença de altos níveis de leptina, somente as crianças asmáticas obesas apresentaram polarização Th1 com ...