Function of adrenomedullin in inflammatory response of liver against LPS-induced endotoxemia.

ABSTRACT

Adrenomedullin (AM) is a hypotension-causing peptide that was originally isolated from human pheochromocytoma cells, and it has been found to be expressed in various organs, including the liver. As the individual physiological and pathophysiological properties of AM peptide in the liver during endotoxemia in vivo has not yet been examined, we investigated this in experimental endotoxemia using heterozygote AM-deficient (AM(+/-)) mice. The AM concentration of AM(+/-) mice was significantly lesser than that of wild-type (WT) mice in lipopolysaccharide (LPS)-induced endotoxemia. After administering LPS, the survival rate for AM(+/-) mice was significantly lower than that for WT mice. Also, expressions of IL-1ß mRNA, and TNF-α mRNA, and NF-κB p65 in the liver were markedly increased and serum ALT greatly elevated in comparison with WT mice. However, supplementation of exogenous AM reversed the deteriorations in mortality and inflammatory responses. Therefore, we conclude that AM plays an important role in regulating systemic inflammation and may be an important intrinsic factor for protecting against liver damage in LPS-induced endotoxemia.