Presence of circulating levels of interferon-gamma, interleukin-10 and tumor necrosis factor-alpha in patients with visceral leishmaniasis.
Experimental murine L. major infection is characterized by the expansion of distinct CD4+ T cell subsets. The Th1 response is related to production of IFN-gamma and resolution of infection, whereas Th-2 response with production of IL-4 and IL-10 and dissemination of infection. The objective of this study was to measure the circulating levels of IFN-gamma, IL-10 and TNF-alpha in patients with visceral leishmaniasis (VL) before, during and at the end of therapy and to examine the association between cytokine levels and activity of VL. Fifteen patients with VL were evaluated. The cytokine determinations were done by using the enzyme-linked immunoassay (ELISA) before, during and at the end of therapy. At baseline, we detected circulating levels of IFN-gamma in 13 of 15 patients (median = 60 pg/ml); IL-10 in 14 of 15 patients (median = 141.4 pg/ml); and TNF-alpha in 13 of 14 patients (median = 38.9 pg/ml). As patients improved, following antimonial therapy, circulating levels of IL-10 showed an exponential decay (y = 82.34 e-0, 10367x, r = -0.659; p < 0.001). IFN-gamma was no longer detected after 7/14 days of therapy. On the other hand, circulating levels of TNF-alpha had a less pronounced decay with time on therapy, remaining detectable in most patients during the first seven days of therapy (y = 36.99-0.933x, r = -0.31; p = 0.05). Part of the expression of a successful response to therapy may, therefore, include reduction in secretion of inflammatory as well as suppressive cytokines. Since IL-10 and IFN-gamma are both detected prior to therapy, the recognized cellular immune depression seen in these patients may be due to biological predominance of IL-10 (type 2 cytokine), rather than lack of IFN-gamma (type 1 cytokine) production.
Division of Infectious Diseases. Escola Paulista de Medicina/Universidade Federal de São Paulo, Brasil. idipa@alphanet.com.br
I M
IM
de Medeiros
A
A
Castelo
R
R
Salomão
D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use; D000965:Antimony / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D007898:Leishmaniasis, Visceral / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008536:Meglumine / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000981:Antiprotozoal Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008536:Meglumine; D000666:Amphotericin B; D007371:Interferon-gamma; D000965:Antimony