maxadilan-protein--insect and Endotoxemia

Sand fly saliva contains maxadilan, a peptide that causes vasodilation and modifies the secretion of pro-inflammatory cytokines by macrophages. We show that 1 to 10 microg maxadilan protected BALB/c mice against a lethal dose of LPS. Maxadilan reduced serum levels of TNF-alpha by approximately tenfold, while it caused a threefold increase in IL-6 and IL-10. The protective effect of maxadilan is partially dependent on its ability to induce IL-10 production since maxadilan did not prevent death from endotoxic shock in IL-10(-/-) mice. Finally, maxadilan is a selective agonist of the pituitary adenylate cyclase-activating peptide (PACAP) type I receptor, and we found that the natural ligand of this receptor (PACAP 38) also protected mice against lethal endotoxemia. These results indicate that activation of the PACAP type I receptor may contribute to the control of systemic inflammation by a mechanism that is partially dependent on IL-10.

Topics: Animals; Endotoxemia; Galactosamine; Insect Proteins; Interleukin-10; Interleukin-6; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neuropeptides; Pituitary Adenylate Cyclase-Activating Polypeptide; Platelet Activation; Psychodidae; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Pituitary Hormone; Salivary Proteins and Peptides; Tumor Necrosis Factor-alpha