Cytokine serum levels in patients infected by human immunodeficiency virus with and without Trypanosoma cruzi coinfection

Rodrigues, Denise Bertulucci Rocha; Correia, Dalmo; Marra, Monica; Giraldo, Luis E.; Lages‐Silva, Eliane; Silva‐Vergara, Mario León; Barata, Cristina Hueb; Rodrigues, Virmondés

doi:10.1590/s0037-86822005000600007

Cited by 20 publications

(12 citation statements)

References 21 publications

(9 reference statements)

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“…63 In HIV-Trypanosoma cruzi coinfection, IL-4 serum levels reached 6200 pg/ml. 64 Intrahepatic concentrations were unknown. We thus took considerable care to demonstrate that during our experiments IL-4 at the concentrations employed was not toxic for hIHFs and had no effect on cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Aoudjehane

Pissaia

Scatton

et al. 2008

Laboratory Investigation

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Interleukin-4 (IL-4) is overexpressed in liver grafts in a context of severe recurrent hepatitis C, during which the development of fibrosis is dramatically accelerated. In this study, we examined the effects of IL-4 on the activation and collagen production of cultured human intrahepatic (myo)fibroblasts (hIHFs), and investigated the underlying mechanisms. The myofibroblastic nature of cells was evaluated morphologically using activation markers (smooth muscle a-actin, vimentin and prolyl 4-hydroxylase). Quiescent hIHFs were obtained by cell incubation in serum-free medium or cell culture on Matrigel. We first analyzed IL-4 receptor expression, STAT-6 activation by IL-4, and STAT-6 inhibition by an anti-IL-4 antibody or by STAT-6 small-interfering RNA (siRNA) transfection. We then focused on collagen production, using quantitative real-time PCR to analyze the effect of IL-4 on the mRNA expression of collagens I, III and IV, and on collagen levels in supernatants of hIHFs, using the Sircol collagen assay. hIHFs cultured in plastic wells appeared to be morphologically activated. The expression of activation markers was reduced by serum deprivation or culture on Matrigel, and restored by IL-4 incubation. The IL-4 receptor was expressed by hIHFs, and STAT-6 was activated following incubation with IL-4. Both anti-IL-4 antibody and STAT-6 siRNA transfection inhibited this activation. The treatment of hIHFs with IL-4 increased the mRNA expression of collagens I, III and IV (Po0.05) and elevated collagen levels in supernatants (P ¼ 0.01 vs untreated cells). Therefore, IL-4 exerts profibrotic effects by activating hIHFs and inducing collagen production and secretion. This effect requires IL4-R binding and STAT-6 activation. IL-4 may thus be involved in accelerated course of fibrogenesis during recurrent hepatitis C.

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Section: Discussionmentioning

confidence: 99%

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Aoudjehane

Pissaia

Scatton

et al. 2008

Laboratory Investigation

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“…Deve ainda ser considerado que a avaliação dos níveis plasmáticos de citocinas representa uma abordagem sistêmica, devendo ser considerados os efeitos de sua diluição no sangue e ainda a possibilidade da contribuição por outros sítios inflamados do organismo. Níveis semelhantes aos encontrados neste estudo foram observados anteriormente 20 . Dados da literatura demonstraram maior produção plasmática de TNF-em pacientes indeterminados 7 e cardíacos 7 25 .…”

Section: B): Níveis Plasmáticos De Ifn- Il-10 E Tnf-em Invidíduos Sunclassified

Associação entre os níveis plasmáticos de TNF-α, IFN-γ, IL-10, óxido nítrico e os isotipos de IgG específicos nas formas clínicas da doença de Chagas crônica

Pissetti

Correia

Braga

et al. 2009

Rev. Soc. Bras. Med. Trop.

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Na década de 90, a doença de Chagas foi considerada pelo Banco Mundial como a doença parasitária mais importante na América Latina, com impacto socioeconômico consideravelmente maior do que os efeitos combinados de outras infecções parasitárias 6 . A doença, cujo agente etiológico é Trypanosoma cruzi, RESUMOA doença de Chagas é uma importante doença parasitária crônica, que acomete cerca de 9-11 milhões de pessoas na América Latina. Provavelmente, uma combinação de fatores relacionados ao parasito e ao hospedeiro podem ser os responsáveis pela patogênese na fase crônica da doença. Dentre os fatores relacionados ao hospedeiro, a resposta imunológica é um parâmetro de especial interesse. Objetivamos avaliar os níveis plasmáticos das citocinas interferon gama, interleucina 10, fator de necrose tumoral alfa e das imunoglobulinas G total, 3 e 4, por ELISA e do óxido nítrico, pela reação de Griess, entre indivíduos soronegativos e soropositivos para Trypanosoma cruzi, com as formas clínicas cardíaca, indeterminada e digestiva. Os indivíduos soropositivos para Trypanosoma cruzi produziram níveis significativamente mais elevados de imunoglobulinas G total e G3. Indivíduos com a forma digestiva apresentam níveis mais elevados de imunoglobulina G4 e interleucina 10. Entretanto, tais indivíduos apresentaram menores níveis de óxido nítrico do que controles. Os resultados sugerem que os maiores níveis de IL-10 observados nos indivíduos com a forma digestiva poderiam contribuir com os maiores níveis de IgG4 específicos observados. Palavras-chaves: Doença de Chagas. Imunoglobulinas. IFN-. IL-10. TNF-. Óxido nítrico. ABSTRACTChagas disease is an important chronic parasitic disease that affects around 9-11 million people in Latin America. A combination of parasite and host-related factors are probably responsible for pathogenesis in the chronic phase of the disease. Among the host-related factors, the immunological response is a parameter of special interest. Our aim here was to evaluate the plasma levels of the cytokines interferon gamma, interleukin 10 and tumor necrosis factor alpha and the immunoglobulins total IgG and its subclasses 3 and 4, by means of ELISA, and the levels of nitric oxide by means of the Griess reaction, among individuals who were seropositive for Trypanosoma cruzi, presenting the cardiac, indeterminate and digestive clinical forms of the disease, and among seronegative individuals. The seropositive individuals produced significantly higher levels of total IgG and IgG-3. Individuals with the digestive form presented higher levels of IgG-4 and interleukin 10. However, these individuals presented lower levels of nitric oxide than the controls did. The results suggest that the higher levels of interleukin 10 observed among individuals with the digestive form may contribute towards the higher levels of the specific IgG-4 that were seen. . A prevalência global da doença foi reduzida de 16-18 milhões de indivíduos infectados na década de 90 para aproximadamente 9 milhões e pode diminuir ainda mais devido às al...

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“…In contrast, differences in the concentration of TNF-α between healthy subjects and patients with mild cardiomyopathy were not always evident, whereas differences between mild and severe diseases were substantiated [140] . Patients who suffered from both HIV infection and Chagas disease presented with higher levels of TNF-α and IL-6 compared with patients with HIV infection only [141] .…”

Section: Inflammation Markersmentioning

confidence: 89%

Chronic Chagas disease: from basics to laboratory medicine

Haberland

Saravia

Wallukat

et al. 2012

Clinical Chemistry and Laboratory Medicine (CCLM)

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Chagas disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America and has huge potential to become a worldwide problem, due to increasing migration, and international tourism, as well as infectant transfer by blood contact and transfusion, intrauterine transfer, and organ transplantation. Nearly 30% of chronically-infected patients become symptomatic, often with a latency of 10–30 years, developing life-threatening complications. Of those, nearly 90% develop Chagas heart disease, while the others manifest gastrointestinal disease and neuronal disorders. Besides interrupting the infection cycle and chemotherapeutic infectant elimination, starting therapy early in symptomatic patients is important for counteracting the disease. This would be essentially supported by optimized patient management, involving risk assessment, early diagnosis and monitoring of the disease and its treatment. From economic and logistic viewpoints, the tools of laboratory medicine should be especially able to guarantee this. After summarizing the basics of chronic Chagas disease, such as the epidemiological data, the pathogenetic mechanisms thought to drive symptomatic Chagas disease and also treatment options, we present tools of laboratory medicine that address patient diagnosis, risk assessment for becoming symptomatic and guidance, focusing on autoantibody estimation for risk assessment and heart marker measurement for patient guidance. In addition, increases in levels of inflammation and oxidative stress markers in chronic Chagas disease are discussed.

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Cytokine serum levels in patients infected by human immunodeficiency virus with and without Trypanosoma cruzi coinfection

Abstract: This study assessed the number of CD4

Cited by 20 publications

References 21 publications

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Associação entre os níveis plasmáticos de TNF-α, IFN-γ, IL-10, óxido nítrico e os isotipos de IgG específicos nas formas clínicas da doença de Chagas crônica

Chronic Chagas disease: from basics to laboratory medicine

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