Schistosoma mansoni antigens alter the cytokine response in vitro during cutaneous leishmaniasis

Schistosoma mansoni infection or associated products are able to down-modulate the type 1 CD4+ T cell inflammatory response characteristic of autoimmune diseases. In this study, we evaluated how S. mansoni antigens altered the immune response that was induced by the soluble Leishmania antigen (SLA) from cutaneous leishmaniasis (CL) patients. Cytokines were measured from the supernatants of peripheral blood mononuclear cell cultures stimulated with SLA. This was performed using the sandwich enzyme linked immunosorbent assay technique in the presence or absence of S. mansoni recombinant antigens Sm29, SmTSP-2 and PIII. The addition of S. mansoni antigens to the cultures resulted in the reduction of interferon gamma (IFN-γ) levels in 37-50 percent of patients. Although to a lesser extent, the antigens were also able to decrease the production of tumour necrosis factor-alpha (TNF-α). We compared patients that either had or did not have reduction in IFN-γ and TNF-α production in cultures stimulated with SLA in the presence of S. mansoni antigens. We found that there was no significant difference in the levels of interleukin (IL)-10 and IL-5 in response to S. mansoni antigens between the groups. The antigens used in this study down-modulated the in vitro proinflammatory response induced by SLA in a group of CL patients through a currently undefined mechanism.

Serum cytokine levels in patients with chronic low back pain due to herniated disc: analytical cross-sectional study / Concentrações plasmáticas de citocinas em pacientes com lombalgia crônica por hérnia de disco: estudo transversal analítico

CONTEXT AND OBJECTIVE: The role of immune response and proinflammatory cytokines in the pathogenesis of chronic pain has been of growing interest. In order to evaluate whether there is any association between disc herniation and elevated cytokine levels, we measured cytokine levels in patients with chronic low back pain and in healthy subjects. DESIGN AND SETTING: Analytical cross-sectional study at the Pain Clinic of Universidade Federal da Bahia (UFBA). METHODS: Cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique on 23 patients with low back pain (G1) and on 10 healthy subjects (G2). RESULTS: The levels of tumor necrosis factor-alpha [TNF-alpha] (G1 = 5.6 ± 2.3 pg/ml; G2 = 1.6 ± 0.5 pg/ml; P = 0.01) and interleukin-6 [IL-6] (G1 = 4.1 ± 3.0 pg/ml; G2 = 0.9 ± 0.4 pg/ml; P = 0.01) were higher in G1. There were no statistically significant differences in relation to interleukin-1 [IL-1] (G1 = 0.5 ± 0.3 pg/ml; G2 = 0.5 ± 0.1 pg/ml; P = 1) or soluble tumor necrosis factor receptor [sTNF-R] (G1 = 572 pg/ml ± 36; G2 = 581 ± 50 pg/ml; P = 0.87). CONCLUSION: The patients with chronic low back pain due to disc herniation presented higher levels of TNF-alpha and IL-6, but not of IL-1 or sTNF-R.

CONTEXTO E OBJETIVO: A função da resposta imunológica e das citocinas pró-inflamatórias na patogênese da dor crônica tem tido interesse crescente. Para avaliar se há correlação entre hérnia de disco e aumento de citocinas, foi medida a concentração de citocinas em pacientes com lombalgia crônica e em indivíduos sadios. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado na Clínica de Dor da Universidade Federal da Bahia (UFBA). MÉTODO: As concentrações de citocinas foram medidas pela técnica de ELISA (enzyme linked immunosorbent assay) em 23 pacientes com lombalgia (G1) e 10 sadios (G2). RESULTADOS: As concentrações de fator-alfa de necrose tumoral [TNF-alpha] (G1 = 5.6 ± 2.3 pg/ml; G2 = 1.6 ± 0.5 pg/ml; P = 0,01) e interleucina-6 [IL-6] (G1 = 4.1 ± 3.0 pg/ml; G2 = 0.9 ± 0.4 pg/ml; P = 0,01) foram maiores no G1. Não houve diferença estatisticamente significante para interleucina-1 [IL-1] (G1 = 0.5 ± 0.3 pg/ml; G2 = 0.5 ± 0.1 pg/ml; P = 1) e receptor solúvel do factor de necrose tumoral [sTNF-R] (G1 = 572 pg/ml ± 36; G2 = 581 ± 50 pg/ml; P = 0,87). CONCLUSÃO: Os pacientes com lombalgia crônica por hérnia de disco apresentam concentrações maiores de TNF-alpha e IL-6, mas não de IL-1 ou sTNF-R.

Citocinas pró-inflamatórias em pacientes com dor neuropática submetidos a tratamento com Tramadol / Proinflammatory cytokines in patients with neuropathic pain treated with Tramadol / Interleucinas proinflamatorias en pacientes con dolor neuropático sometidos a tratamiento con Tramadol

JUSTIFICATIVA E OBJETIVOS: As citocinas pró-inflamatórias têm função importante na fisiopatologia das síndromes dolorosas neuropáticas. O objetivo desse estudo foi avaliar os níveis plasmáticos de citocinas pró-inflamatórias antes e após o tratamentocom tramadol em pacientes com hérnia discal e síndrome do túnel do carpo e compará-los com indivíduos normais.MÉTODO: Investigou-se 38 pacientes com dor neuropática por hérnia discal ou síndrome do túnel do carpo. Todos os pacientes foram tratados com tramadol de liberação controlada (100 mg em 12h) durante 10 dias. Realizaram-se coletas de sangue venoso (5 mL), no período matutino, antes do tratamento e no 11º dia e as amostras foram armazenadas até análise (-70ºC). Foram utilizados testes enzimáticos ELISA para dosagem de citocinas plasmáticas (TNF-α, IL-1, IL-6) e receptores sTNF-R1, (R & D Systems). Realizou-se dosagem de citocinas em soro de 10 voluntários sadios. RESULTADOS: A concentração de TNF-α antes (5,8 ± 2,8 pg.mL-1) foi significativamente maior que após o tramadol (4,8 ± 2,1 pg.mL-1; p = 0,04, Teste Mann-Whitney). Não houve diferença significativa de IL-1β, IL-6 e sTNF-R1 antes e após o tratamento. As concentrações plasmáticas de TNF-α (sadios: 1,4 ± 0,5; pacientes com dor: 5,8 ± 2,8 pg.mL-1; p = 0.01) e IL-6 (sadios: 1,2 ± 0,8; pacientes com dor: 3,5 ± 2,6 pg.mL-1; p = 0,01) foram significativamente maiores nos pacientes com dor neuropática que nos voluntários, Teste de Mann-Whitney. CONCLUSÕES: Nos pacientes com hérnia discal e síndrome do túnel do carpo as concentrações plasmáticas de TNF-α e IL-6 foram maiores que em voluntários sadios, não havendo diferença das concentrações de sTNF-R e IL-1β. Houve redução da concentraçãoplasmática de TNF-α após tratamento com tramadol (100 mg em 12h), mas não de IL-6, sTNF-R e IL-1β.

BACKGROUND AND METHODS: Proinflammatory cytokines play an important role in the pathophysiology of neuropathic pain syndromes. The objective of this study was to evaluate plasma levels of proinflammatory cytokines before and after treatment with tramadol in patients with herniated intervertebral disks and carpal tunnel syndrome, and to compare them with normal individuals. METHODS: Thirty-eight patients with neuropathic pain secondary to herniated intervertebral disks or carpal tunnel syndrome participated in this study. All patients were treated with controlled release tramadol (100 mg every 12 hours) for 10 days. Venous blood (5 mL) was collected in the morning, before treatment and on the 11th day, and stored (-70º C) until analysis. ELISA was used to determine the plasma levels of cytokines (TNF-α, IL-1, IL-6) andreceptors sTNF-R1 (R & D Systems). Plasma levels of cytokines of 10 healthy volunteers were also determined. RESULTS: The concentration of TNF-α before (5.8 ± 2.8 pg.mL-1) was significantly higher than after treatment with tramadol (4.8 ± 2.1 pg.mL-1; p = 0.04, Mann-Whitney test). The levels of IL-1β, IL-6, and sTNF-R1 before and after treatment with tramadol showed nosignificant differences. Plasma levels of TNF-α (healthy individuals: 1.4 ± 0.5; pain patients: 5.8 ± 2.8 pg.mL-1; p = 0.01) and IL-6 (healthy individuals: 1.2 ± 0.8; pain patients: 3.5 ± 2.6 pg.mL-1; p = 0.01) were significantly higher in patients with neuropathic pain, Mann-Whitney Test. CONCLUSIONS: In patients with herniated intervertebral disks and carpal tunnel syndrome, plasma levels of TNF-α and IL-6 werehigher than in healthy volunteers, while differences in the concentrations of sTNF-R and IL-1β were not observed. Plasma levels of TNF-α, but not of IL-6, sTNF-R, and IL-1β, decreased after treatment with tramadol (100 mg every 12 hours).

JUSTIFICATIVA Y OBJETIVOS: Las interleucinas proinflamatorias tienen una función importante en la fisiopatología de los síndromes dolorosos neuropáticos. El objetivo de este estudio, fue evaluar los niveles plasmáticos de interleucinas proinflamatorias antes y después del tratamiento con tramadol en pacientes con hernia de disco y síndromedel túnel del carpo, y compararlos con individuos normales. MÉTODO: Se investigaron 38 pacientes con dolor neuropático por hernia de disco o síndrome del túnel del carpo. Todos los pacientes fueron tratados con tramadol de liberación controlada (100 mg en 12h) durante 10 días. Se realizaron muestras de sangre venosa (5 mL), por la mañana, antes del tratamiento y en el 11º día, y las mismas se almacenaron para ser analizadas (-70ºC). Se utilizaron test enzimáticos ELISA para la dosificación de las interleucinas plasmáticas (TNF-α, IL-1, IL-6) y receptores sTNFR1, (R & D Systems). Se realizó la dosificación de interleucinasen suero de 10 voluntarios sanos. RESULTADOS: La concentración de TNF-α antes (5,8 ± 2,8 pg.mL-1) fue significativamente mayor que después del tramadol (4,8 ± 2,1 pg.mL-1; p = 0,04, Test de Mann-Whitney). No hubo diferencia significativa de IL-1β, IL-6 y sTNF-R1 antes y después del tratamiento. Las concentraciones plasmáticas de TNF-α (sanos: 1,4 ± 0,5; pacientes con dolor: 5,8 ± 2,8 pg.mL-1; p = 0.01) y IL-6 (sanos: 1,2 ± 0,8; pacientes con dolor: 3.5 ± 2,6 pg.mL-1; p = 0,01) fueron significativamente mayores en los pacientes con dolor neuropático que en los voluntarios, test de Mann-Whitney. CONCLUSIONES: En los pacientes con hernia discal y síndrome del túnel del carpo, las concentraciones plasmáticas de TNF-α yIL-6, fueron más elevadas que en los voluntarios sanos, no habiendo ninguna diferencia en las concentraciones de sTNF-R y IL-1β...

Avaliaçäo da resposta imune celular em pacientes com candidíase recorrente / Evaluation of cellular immune response in patients with recurrent candidiasis

A candidíase recorrente cutânea ou mucosa é caracterizada pela ocorrência de, no mínimo, 4 episódios de candidíase no período de um ano. Näo säo conhecidos os fatores que levam à recorrência desta infecçäo. O presente estudo avaliou a resposta linfoproliferativa e a produçäo de IFN-g de pacientes com candidíase recorrente. Os índices de estimulaçäo da resposta linfoproliferativa em culturas de células de pacientes com candidíase recorrente estimuladas com antígeno de Candida albicans, PPD e TT foram respectivamente de 6±8, 17±20 e 65±30. A adiçäo de anticorpo monoclonal anti-IL-10 às culturas de células de 6 pacientes aumentou a resposta linfoproliferativa de 735±415 para 4143±1746 cpm. A produçäo de IFN-g em culturas de células estimuladas com antígeno de Candida, foi 162±345pg/ml. Pacientes com candidíase recorrente apresentam uma deficiência na resposta linfoproliferativa e na produçäo de IFN-g, podendo a resposta imune celular ao antígeno de Candida ser restaurada parcialmente através da neutralizaçäo da IL-10 in vitro

Evaluation of IFN-gamma and TNF-alpha as immunological markers of clinical outcome in cutaneous leishmaniasis

To evaluate if IFN-gamma and TNF-alpha levels could be used as markers of therapeutic response in cutaneous leishmaniasis, 54 patients with history of one ulcerated cutaneous lesion, with up to 30 days onset, were enrolled in the study. IFN-gamma and TNF-alpha were measured by ELISA in lymphocyte cultures supernatant before and 60 days after initiating therapy. Cure was considered to be a complete healing of lesion 60 days after treatment. IFN-gamma and TNF-alpha levels were similar in both groups of patients before therapy. There was a tendency to increase IFN-gamma levels in patients that were cured in 60 days, however the values did not reach statistical significance. In both groups of patients, TNF-alpha levels were similar before therapy and fell significantly after treatment, irrespective of cure or maintenance of active lesion.

Avaliaçäo clínica do edema labial / Clinical evaluation of the lip swelling

Objetivo: O edema labial é uma manifestaçäo clínica habitualmente avaliada e tratada por especialistas em alergia e, em algumas situaçöes, constitui um desafio diagnóstico. Métodos: Apresentaçäo de um caso em adolescente com edema labial. Resultados: O exame anatomopatológico firmou o diagnóstico de S. Melkersson-Rosental. Conclusöes: O presente artigo faz uma revisäo sobre o tema e apresenta um caso clínico, onde säo discutidos o diagnóstico diferencial e a abordagem terapêutica de um caso de edema labial

Immunoregulation in leishmaniasis

Leishmaniasis is caused by protozoa of the genus Leishmania which are transmitted to humans by the bite of infected phlebotomine sandflies. Four different clinical forms of leishmaniasis are well characterized: cutaneous leishmaniasis, mucosal leishmaniasis, diffuse cutaneous leishmaniasis and visceral leishmaniasis. Recovery from and resistance to disease in leishmaniasis are strongly associated to effective T cell responses, with no recognized participation of specific antibodies. Protective immunity against Leishmania has been related, predominantly, to IFN-gamma producing CD4+ Th1 helper T cells. IFN-gamma is known as the macrophage activating factor and addition of this cytokine to Leishmania-infected macrophages results in Leishmania killing. There are also indications of the participation of cytotoxic CD8+ T cells in the control of Leishmania infection. The immunological responses are different in the clinical forms of leishmaniasis. Patients with visceral leishmaniasis have absence of lymphocyte proliferative response and IFN-gamma production upon leishmanial antigen stimulation, and there is mRNA for IL-10 and IL-4 in peripheral blood mononuclear cells. In the present study it is documented that lymphocyte proliferation and IFN-gamma production are restored by addition to the cultures of either nonoclonal antibody anti-IL-10 or IL-12. These data are evidence of Th2 activation in visceral leishmaniasis and indicate that cytokine or cytokine antagonists may be used as therapeutic adjuvants in visceral leishmaniasis. Different from visceral leishmaniasis, patients with cutaneous or mucosal leishmaniasis have a strong T cell response to leishmania antigen. Such response is characterized by delayed type hypersensitivity, lymphocyte proliferation and production of cytokines such as IL-2 and IFN-gamma. In this study the cytotoxic response in patients with tegumentary leishmaniasis was documented by the ability of PBMC from cutaneous and mucosal leishmaniasis patients to kill K562 tumor target cells. Moreover the ability of cytokine and cytokine antagonist in modulating cytotoxic functions was tested. Evidence was found that antigen-induced cytotoxicity against K562 tumor target cell was modulated by both IL-10 and TGF-beta. When L.amazonensis antigen stimulated patient PBMC were tested in the presence of TGF-beta there was a marked reduction in the cytotoxicity against K562...

Efeito da pirazinamida sobre a resposta imune celular humana / Effect of pyrazinamide on human cellular immune response

A incorporaçäo da pirazinamida (PZA) ao esquema quimioterápico da tuberculose permitiu que o seu tratamento fosse encurtado para seis meses. A despeito da eficácia da PZA in vivo, experências in vitro com esta droga näo demonstram atividade bactericida relevante. Com a finalidade de avaliar o efeito da PZA sobre a resposta imune, foram realizados testes cutâneos de hipersensibilidade tardia com PPD e antígeno de Candida albicans ou testes de transformaçäo lifoblástica, em 33 pacientes com tuberculose pulmonar antes e durante o tratamento: 21 em uso de PZA e 12 controles em quimioterapia sem este fármaco. Encontramos transformaçäo linfoblástica basal de 905 ñ 302 cpm nos doentes que usavam PZA, em contraste com 258 ñ 147 cpm anteriores à quimioterapia, e 323 ñ 90 cpm no grupo tratado sem PZA. Estas diferenças säo estatisticamente significantes. Ocorreu também uma tendência de maior reatividade cutânea em pacientes submetidos à PZA, mas com diferenças näo significantes. Nossos resultados podem explicar, em parte, como esta droga age contra o M. tuberculosis e indicam que investigaçäo complementar apropriada deve ser feita para avaliar a possibilidade de emprego da PZA em outras doenças, em que a resposta imunecelular tenha papel importante nos mecanismo de defesa do hospedeiro