INTERLEUKIN-10 PRODUCTION CORRELATES WITH PATHOLOGY IN HUMAN LEISHMANIA-DONOVANI INFECTIONS

We have found that an important Th2 cytokine, IL-10, is produced by ti ssues from patients acutely infected with Leishmania donovani. In all individuals tested, IL-10 mRNA production was increased in lymph nodes taken during acute disease over that observed in postacute samples. I n contrast, both pre- and posttreatment lymph nodes had readily detect ed MRNA for IFN-gamma and IL-2. A down-regulating effect of IL-10 on l eishmania-induced proliferative responses was demonstrated when Hu rIL -10 was added to cultures of PBMC from clinically cured individuals. P BMC from individuals with acute visceral leishmaniasis responded to st imulation with leishmania lysate by producing IL-10 MRNA. Simultaneous ly cultured PBMC collected from the same patients after successful che motherapy produced no detectable Ll-10 MRNA after leishmania antigen s timulation. Neutralizing anti-IL-10 mAb added to PBMC from patients wi th acute visceral leishmaniasis markedly increased the proliferative r esponse to leishmania lysate. Finally, we observed mRNA for IL-10 and IFN-gamma concurrently in a lesion from a patient with post-kala-azar dermal leishmaniasis (PKDL). These results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytoki ne in the regulation of immune responsiveness during visceral leishman iasis.