Cytokine profile and pathology in human leishmaniasis

The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-<FONT FACE="Symbol">g</font> is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-<FONT FACE="Symbol">g</font> production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-<FONT FACE="Symbol">g</font> production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-<FONT FACE="Symbol">g</font> production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-<FONT FACE="Symbol">g</font> production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-<FONT FACE="Symbol">g</font> are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-<FONT FACE="Symbol">g</font> levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 ± 26 pg/ml). This response was restored by IL-12 (308 ± 342 pg/ml) and anti-IL-10 mAb (380 ± 245 pg/ml) (P<0.05). Later during the disease, high levels of IFN-<FONT FACE="Symbol">g</font> and TNF-<FONT FACE="Symbol">a</font> are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-<FONT FACE="Symbol">a</font> levels (366 ± 224 pg/ml before treatment vs 142 ± 107 pg/ml after treatment, P = 0.02). Although production of IFN-<FONT FACE="Symbol">g</font> and TNF-<FONT FACE="Symbol">a</font> might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis