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
leishmaniasis; human leishmaniasis; cytokines; pathology; immunological responses
