Role of interleukin-4 and prostaglandin E2 in Leishmania amazonensis infection of BALB/c mice

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 PGE2 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 × 106 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 × 106 inoculum. However, IL-4−/− mice developed smaller lesions upon infection with 105, 104 or 103 parasites than IL-4+/+ mice. The resistance of IL-4−/− correlated with higher Th1 response, compared to IL-4+/+ upon infection with 104L. amazonensis. IL-4+/+ mice treated with indomethacin, an inhibitor of PGE2 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 PGE2 are susceptibility factors to L. amazonensis infection.