Role of interleukin-4 and prostaglandin E 2 in Leishmania amazonensis infection of BALB/c mice

Abstract

The role of cytokines in Leishmania amazonensis experimental infection has not been as well studied as in Leishmania major infection model. Here we investigated the role of interleukin (IL)-4 and PGE 2 in L. amazonensis infection of susceptible BALB/c mice. IL-4 deficient (−/−) or wild-type (+/+) BALB/c mice were infected with different inocula of L. amazonensis. Two weeks after infection with 5 × 10 6 promastigotes/footpad, the production of interferon (IFN)-gamma upon L. amazonensis antigen stimulation was significantly higher in lymph node cell cultures of IL-4−/− mice than in IL-4+/+ mice. The levels of anti-leishmania IgG2a antibodies were also significantly higher in serum from IL-4−/− mice. In contrast, the levels of IgG1 antibodies were increased in IL-4+/+ mice and almost undetectable in IL-4−/− mice. Despite the increased Th1 response, lesions of IL-4−/− BALB/c mice progressed similarly to those of IL-4+/+ mice upon infection with the 5 × 10 6 inoculum. However, IL-4−/− mice developed smaller lesions upon infection with 10 5, 10 4 or 10 3 parasites than IL-4+/+ mice. The resistance of IL-4−/− correlated with higher Th1 response, compared to IL-4+/+ upon infection with 10 4 L. amazonensis. IL-4+/+ mice treated with indomethacin, an inhibitor of PGE 2 synthesis, during the first 3 weeks of infection developed smaller lesions and lower parasitic load when compared to the control group. The lesions of indomethacin-treated groups contained mostly macrophages without vacuoles and small or absent necrotic areas. These results indicate that IL-4 and PGE 2 are susceptibility factors to L. amazonensis infection.