American cutaneous leishmaniasis: In situ immune response of patients with recent and late lesions

TNF­α, IFN­Î³, IL­10, IL­17, CD68 and CD57 were evaluated in biopsies of patients with American cutaneous leishmaniasis living in Sorocaba, Brazil. The analyses were performed considering the time of lesions from 23 patients with recent lesions (Group I) and 19 patients with late lesions (Group II). All patients were infected with Leishmania (Viannia) braziliensis. Immunostaining cells for CD68, CD57, TNF­ α, IFN­Î³, IL­10 and IL­17 were performed by immunohistochemistry. Except for CD68 and IL­17, the distribution of in situ for CD57, IL­10, TNF­α and IFN­Î³ showed that patients with recent lesions expressed higher levels than those with late lesions. The comparison of cytokine expression/group showed that IL­10 was significantly higher than IL­17 and IFN­Î³ (similar data were shown in IL­17 compared with TNF­α), suggesting an immunological balance between inflammatory­anti­inflammatory agents. This balance was similar for two groups of patients. In conclusion, these data suggested that (i) patients from Group I had recent lesions (in the beginning of chronic phase) compared to those from Group II and (ii) the modulation of inflammatory response in patients with recent American cutaneous leishmaniasis was correlated with IL­10 expression in skin lesions preventing the development of mucosal forms. The parasite treatment also prevented the evolution of severe forms.

TNF-α, IFN-γ, IL-10, IL-17, CD68 e CD57 foram avaliados em biópsias de pacientes com leishmaniose tegumentar americana residentes em Sorocaba, Brasil. As análises foram realizadas considerando o tempo de lesão de 23 pacientes com lesões recentes (Grupo I) e 19 pacientes com lesões tardias (Grupo II). Todos os pacientes foram infectados com Leishmania (Viannia) braziliensis. As células de imunocoloração para CD68, CD57, TNF-α, IFN-γ, IL-10 e IL-17 foram realizadas por imuno-histoquímica. Exceto para CD68 e IL-17, a distribuição in situ de CD57, IL-10, TNF-α e IFN-γ mostrou que pacientes com lesões recentes expressavam níveis mais altos do que aqueles com lesões tardias. A comparação da expressão / grupo de citocinas mostrou que a IL-10 foi significativamente maior que a IL-17 e IFN-γ (dados semelhantes foram mostrados na IL-17 em comparação com o TNF-α), sugerindo um equilíbrio imunológico entre agentes inflamatórios e anti-inflamatórios . Esse equilíbrio foi semelhante para dois grupos de pacientes. Em conclusão, esses dados sugeriram que (i) pacientes do grupo I apresentavam lesões recentes (no início da fase crônica) em comparação com os do grupo II e (ii) a modulação da resposta inflamatória em pacientes com leishmaniose tegumentar americana recente estava correlacionada com Expressão da IL - 10 em lesões cutâneas impedindo o desenvolvimento de formas mucosas. O tratamento do parasita também impediu a evolução de formas graves.

Cerebral and ocular toxoplasmosis related with IFN-y, TNF-a, and IL-10

This study analyzed the synthesis of Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), and Interleukin 10 (IL-10) in chronically infected patients which developed the symptomatic disease as cerebral or ocular toxoplasmosis. Blood from 61 individuals were divided into four groups: Cerebral toxoplasmosis/AIDS patients (CT/AIDS group) (n = 15), ocular toxoplasmosis patients (OT group) (n = 23), chronic toxoplasmosis individuals (CHR group) (n = 13) and healthy individuals (HI group) (n = 10). OT, CHR, and HI groups were human immunodeficiency virus (HIV) seronegative. The diagnosis was made by laboratorial (PCR and ELISA) and clinical subjects. For cytokine determination, peripheral blood mononuclear cells (PBMC) of each patient were isolated and stimulated in vitro with T. gondii antigen. IFN-γ, TNF-α, and IL-10 activities were determined by ELISA. Patients from CT/AIDS and OT groups had low levels of IFN-γ when were compared with those from CHR group. These data suggest the low resistance to develop ocular lesions by the low ability to produce IFN-γ against the parasite. The same patients, which developed ocular or cerebral toxoplasmosis had higher TNF-α levels than CHR individuals. High TNF-α synthesis contribute to the inflammatory response and damage of the choroid and retina in OT patients and in AIDS patients caused a high inflammatory response as the TNF-α synthesis is not affected since monocytes are the major source this cytokine in response to soluble T. gondii antigens. IL-10 levels were almost similar in CT/AIDS and OT patients but low when compared with CHR individuals. The deviation to Th2 immune response including the production of anti-inflammatory cytokines, such as IL-10 may promote the parasite's survival causing the tissue immune destruction. IL-10 production in T. gondii-infected brains may support the persistence of parasites as down-regulating the intracerebral immune response. All these indicate that OT and CT/AIDS patients produced low levels of IL-10 (Th2 response) and IFN-γ (Th1 response). They produced high TNF-α suggesting a high inflammatory response triggered by the parasite.