Enkephalins as a therapeutic intervention for visceral leishmaniasis

Visceral leishmaniasis (VL) is a neglected tropical disease with high incidence of mortality and morbidity. The emergence of drug resistant parasites, severe toxic effects of existing anti-leishmanials, and nonexistence of an effective vector control measures and human vaccine(s) against VL poses a serious problem to VL treatment and control. In VL, the disease pathogenicity is correlated with the up-regulation of Th2 cytokines (IL-4, IL-10 and TGF-β), which can deactivate macrophages and favors the growth of intracellular parasite and disease clearance is expedited through the increased levels of Th1 mediated cytokines (IL-12) which can activate macrophages to release IFN-γ; stimulates inducible NOS to release NO and kills the leishmania parasite. Enkephalins (ENKs), are endogenous neuropeptides with immune stimulatory properties. ENKs and its fragmented peptides at lower concentrations activates Th1 type cytokines and inhibits Th2 type cytokines, which may be helpful in parasite clearance. ENKs in combination with currently available anti-leishmanial drugs may be helpful in reducing the toxicity and duration of therapy. Therefore, we hypothesized that the ENKs alone or in combination with current recommended anti-leishmanial agents might be effective in the treatment of VL with enhanced efficacy and safety profile.