VARIATION OF CYTOKINE PATTERNS RELATED TO THERAPEUTIC RESPONSE IN DIFFUSE CUTANEOUS LEISHMANIASIS

Diffuse cutaneous leishmaniasis is a rare entity characterized by diss eminated cutaneous nodules associated with specific anergy to leishman ial antigens. A low but not absent IFN-gamma expression by cells prese nt in cutaneous lesions has been documented during the active phase of diffuse cutaneous leishmaniasis. In this study we confirm this observ ation, and extend it by showing a similar pattern in peripheral blood mononuclear cells and the variation of mRNA cytokine expression patter n during different stages of the disease. During active disease, patie nts did not express mRNA for IFN-gamma, while expressing mRNA for IL-2 , IL-4, and IL-10. In contrast, an expression of IFN-gamma and low IL- 10 was observed after treatment-induced transient healing of cutaneous lesions. In three patients we have been able to analyze a third PBMC sample obtained after clinical relapse, documenting in all of them dec reased IFN-gamma expression with no expression of IL-10. Although ther e was an association between the appearance of IFN-gamma expression an d clinical improvement, with marked expression of IFN-gamma mRNA and d ecreased expression of mRNA for IL-10 after treatment, this was not su fficient to prevent relapse in these patients. Therefore, it is possib le that factors other than the cytokines characteristic of the Th1 and Th2 balance are implicated in the inability of diffuse cutaneous leis hmaniasis patients to mount an anti-leishmania immune response causing clinical improvement. (C) 1996 Academic Press, Inc.