INCREASED EXPRESSION OF PROINFLAMMATORY CYTOKINES IN CHRONIC LESIONS OF HUMAN CUTANEOUS LEISHMANIASIS

The nature of the host cellular immune response largely determines the expression of disease following infection with the intracellular prot ozoans Leishmania spp. In experimental animals control and resolution of infection are mediated by gamma interferon and tumor necrosis facto r alpha (TNF-alpha), whereas disease progression is associated with th e production of interleukin 4 (IL-4), IL-5, IL-10, and transforming gr owth factor beta (TGF-beta). We have analyzed the profile of cytokine gene expression directly in the lesions of 13 patients with localized cutaneous leishmaniasis due to Leishmania mexicana. All but one patien t had a single lesion, and the time of evolution ranged from 8 days to 18 months. Cytokine gene expression was quantitated by reverse transc riptase PCR and interpolation from a standard curve. Gamma interferon, TNF-alpha, IL-1 alpha, IL-6, IL-10, and TGF-beta gene expression was present in all samples. IL-3 and IL-4 gene expression was barely detec table in 1 and 3 of 13 samples, respectively. IL-2 and IL-5 mRNAs were not found. A significant increase in the expression of IL-1 alpha, TN F-alpha, IL-10, and TGF-beta was observed in late lesions (greater tha n or equal to 4 months) compared with that in early lesions (less than or equal to 2 months). Because of their inhibitory effects on macroph age function, the expression of IL-10 and TGF-beta may play a role in the immunopathogenesis of chronic cutaneous leishmaniasis.