The PACAP-type I receptor agonist maxadilan from sand fly saliva protects mice against lethal endotoxemia by a mechanism partially dependent on IL-10

Eur J Immunol. 1998 Oct;28(10):3120-7. doi: 10.1002/(SICI)1521-4141(199810)28:10<3120::AID-IMMU3120>3.0.CO;2-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Endotoxemia / chemically induced
  • Endotoxemia / prevention & control*
  • Galactosamine / pharmacology
  • Insect Proteins / pharmacology*
  • Interleukin-10 / blood
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-6 / blood
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neuropeptides / pharmacology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Platelet Activation / drug effects
  • Psychodidae / chemistry
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Pituitary Hormone / agonists*
  • Salivary Proteins and Peptides / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adcyap1 protein, mouse
  • Insect Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • 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
  • Interleukin-10
  • maxadilan protein, insect
  • Galactosamine