Cytokine patterns in the pathogenesis of human leishmaniasis.

The host response to infection appears to be regulated by spe- cific patterns of local cytokine production. In the mouse, resis- tance to many pathogens including Leishmania is associated with a THl cytokine profile, IL-2 and IFN-,y; whereas suscepti- bility to infection is associated with production of TH2 cyto- kines, IL4, IL-5, and IL-10. To determine the cytokine patterns of the local immune response to Leishmania infection in humans, we used the polymerase chain reaction to compare cytokine mRNAs in biopsy specimens of American cutaneous leishmaniasis. In localized cutaneous leishmaniasis and the Montenegro delayed-type hypersensitivity reaction, type 1 cytokine mRNAs such as IL-2, IFN-y, and lymphotoxin were relatively predominant. In the chronic and destructive mucocu- taneous form of leishmaniasis, there was a mixture of type 1 and type 2 cytokines, with a striking abundance of IL4 mRNA in lesions. These results suggest that clinical course of infection with Leishmania braziliensis in man is associated with specific local patterns of cytokine production. (J. Clin. Invest. 1993 . 9 :1390-1395.) Key words: cytokines -interleukin 4 * leish- maniasis * polymerase chain reaction * T lymphocytes recur or progress as a more chronic form. This scenario is exemplified in the human response to the parasite Leishmania braziliensis. The most common clinical form ofdisease caused by L. braziliensis is localized cutaneous leishmaniasis (LCL),' characterized by single or multiple ulcerated dermal lesions that usually heal spontaneously. However, in 2-5% of LCL patients in Brazil, a chronic mucocutaneous (MCL) form arises in which there is severe and progressive destruction ofthe nasal, oral, and/or pharyngeal mucous membranes.