Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response

BACKGROUND: Apis mellifera venom, which has already been recommended as an alternative anti-inflammatory treatment, may be also considered an important source of candidate molecules for biotechnological and biomedical uses, such as the treatment of parasitic diseases. METHODS: Africanized honeybee venom from Apis mellifera was fractionated by RP-C18-HPLC and the obtained melittin was incubated with promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Cytotoxicity to mice peritoneal macrophages was evaluated through mitochondrial oxidative activity. The production of anti- and pro-inflammatory cytokines, NO and H(2)O(2) by macrophages was determined. RESULTS: Promastigotes and intracellular amastigotes were susceptible to melittin (IC(50) 28.3 μg.mL(−1) and 1.4 μg.mL(−1), respectively), but also showed mammalian cell cytotoxicity with an IC(50) value of 5.7 μg.mL(−1). Uninfected macrophages treated with melittin increased the production of IL-10, TNF-α, NO and H(2)O(2). Infected melittin-treated macrophages increased IL-12 production, but decreased the levels of IL-10, TNF-α, NO and H(2)O(2). CONCLUSIONS: The results showed that melittin acts in vitro against promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Furthermore, they can act indirectly on intracellular amastigotes through a macrophage immunomodulatory effect.