Cutaneous Leishmaniasis

Transforming growthfactor (TGF)-,8 has several downregulatoryfunctions on the immune systenm inhibition ofinterleukin-2 receptor induction, decrease of interferon-yinduced class II antigen expression, inhibition of macrophage activation, as weUl as cytotoxic and lymphokineactivated kilter cell generation. TGF-(8 has also been recognized as an important immunoregulator in murine leishmaniasis, for which it increases susceptibility to disease. In the present study we evaluate the involvement of TGF-j8 in human leishmaniasis in vitro and in patients with cutaneous leishmaniasis. Human macrophages produce active TGF-,3 after infection by Leishmania amazonensis (480 ± 44.7 pg/ml mean ± SEM), L. donovani chagasi (295 + 7.6 pg/ml), or L. braziliensis (196 ± 15.7 pg/ml). When TGF-g3 was added to cultures of human macrophages infected with L. braziliensis it led to an increase of approximately 50% in parasite numbers as compared with untreated cultures. Exogenous TGF1 added to macrophage cultures was able to reverse the effect of interferon-y in controUing Leishmaniagrowth. Even at 100 IU/ml interferon-y the presence ofTGF8 increases the number of intracellular parasites. On the other hand, TNF-a at high concentration (100 IU/ml) totaly blunts the suppressive effect of TGF-4 Immunostaining for TGF-13 was observed in the dermis, produced by fibroblasts and occasionally by inflammatory cells in the biopsies from human leishmaniasis lesions, being present in most of the biopsies taken from patients with early cutaneous leishmaniasis (less than 2 months of ulcer development) and in cases of active mucosal leishmaniasis. Taken together these observations suggest an important rolefor TGF-18 in human leishmaniasis, with its production by infected macrophages being probably related to parasite establishment in the early stages of the disease. (Am J Pathol 1995, 147:947-954)