The role of cyclosporin A, leptin, and FK-506 in Leishmania major infections in mice

Abstract

The immune response to some pathogenic microorganisms fails to protect the individual from severe infection and disease. Subsets of lymphocytes play a role in the outcome of an infection, particularly two subsets of T cells, called T-helper ( TH1 and TH2) lymphocytes. When preferentially stimulated, the TH2 cells are often inadequate or inappropriate in controlling certain microbes and as a result serious infection develops. The TH1 response, on the other hand, may result in the resolution of the severe infection. In this study, we attempted to determine if leptin, cyclosporin A (CsA), and/or FK506 could switch the immune response in Leishmania major infected BALB/c mice from a TH2 to a TH1 type response thereby protecting them from severe disease. Groups of mice were infected with L. major and treated prophylactically with one of the above three drugs. The mice were compared to non-treated, infected animals using a variety of observations including ulcer development, footpad size, quantification of L. major in tissues and cytokine production. Data suggests that FK506 and CsA are very effective immunomodulatory drugs, while the amount of leptin is critical for the balance between TH1 and TH2.