TRANSFORMING GROWTH-FACTOR-BETA IN TEGUMENTARY LEISHMANIASIS

1. The course of infection with the protozoan parasite Leishmania is d etermined in part by its early replication in macrophages, the exclusi ve host cells for these organisms. Resistance to and recovery from lei shmanial infection is related to cell-mediated immune responses in all forms of human and murine leishmaniasis. 2. Factors contributing to t he early inhibition or proliferation of Leishmania are poorly understo od, but cytokines such as IFN gamma, IL-10 or transforming growth fact or beta (TGF-beta) are known to influence the replication of Leishmani a in macrophages. 3. TGF-beta is a multipotential cytokine with divers e effects on cells of the immune system, including down-regulation of certain macrophage functions. Infection of murine or human macrophages by Leishmania induces the production of active TGF-beta. Recombinant TGF-beta added to murine or human macrophage cultures leads to increas ed intracellular replication of Leishmania. Exogenous TGF-beta adminis tered in vivo promotes enhancement of infection, whereas its neutraliz ation by monoclonal antibodies decreases the level of in vitro infecti on, and protects susceptible mice. 4. Susceptible animals treated with anti-TGF-beta monoclonal antibodies change their immune response, not increasing the expression of IL-4 while increasing the expression of IFN gamma mRNA in their draining lymph nodes. Resistant animals treate d with TGF-beta also change their pattern of immune response as indica ted by an increase of the important Th2 cytokine IL-10 mRNA in the dra ining lymph node.