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

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.

journal_name

Eur J Immunol

authors

Bozza M,Soares MB,Bozza PT,Satoskar AR,Diacovo TG,Brombacher F,Titus RG,Shoemaker CB,David JR

doi

10.1002/(SICI)1521-4141(199810)28:10<3120::AID-IMM

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

3120-7

issue

10

eissn

0014-2980

issn

1521-4141

journal_volume

28

pub_type

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