VIP: an agent with license to kill infective parasites.

Antimicrobial peptides are small, cationic, and amphipathic peptides of variable length, sequence, and structure. They are effector molecules of innate immunity with microbicidal and both pro- or anti-inflammatory activities. Vasoactive intestinal polypeptide (VIP) and the structurally related pituitary adenylate cyclase-activating polypeptide (PACAP) are well-known immunomodulators. On the basis of their cationic and amphipathic structures, resembling antimicrobial peptides, we propose that their immune role could also include a direct lethal effect against pathogens. We thus investigated the potential antiparasitic activities of VIP and PACAP against the African trypanosome Trypanosoma brucei (T. brucei). Both peptides killed the bloodstream (infective) form but not the insect (noninfective) form of the parasite. VIP and PACAP caused complete destruction of the parasite integrity through a mechanism involving their entry and accumulation into the cytosol. These results provide the basis for further studies of these and other structurally related peptides as alternative treatments for parasitic diseases mainly with associated drug resistances.