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

Ryoichi Saito1, Tatsuo Shimosawa, Takehide Ogihara

  • 1Department of Microbiology and Immunology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Japan.

Insights

Adrenomedullin (AM) peptide protects the liver during endotoxemia. Lower AM levels in deficient mice correlated with increased inflammation and mortality, which exogenous AM supplementation reversed.

Area of Science:

  • Immunology
  • Endocrinology
  • Hepatology

Background:

  • Adrenomedullin (AM) is a peptide known for its hypotensive effects.
  • AM is expressed in various organs, including the liver.
  • The role of AM in liver pathophysiology during endotoxemia is not well understood.

Purpose of the Study:

  • To investigate the physiological and pathophysiological roles of AM in the liver during lipopolysaccharide (LPS)-induced endotoxemia.
  • To examine the impact of AM deficiency on liver function and survival rates in a mouse model.

Main Methods:

  • Utilized heterozygote AM-deficient (AM(+/-)) and wild-type (WT) mice in an LPS-induced endotoxemia model.
  • Measured AM concentrations, survival rates, and liver markers (IL-1β mRNA, TNF-α mRNA, NF-κB p65, ALT).
  • Administered exogenous AM to assess its protective effects.

Main Results:

  • AM concentrations were significantly lower in AM(+/-) mice compared to WT mice during endotoxemia.
  • AM(+/-) mice exhibited significantly lower survival rates and increased liver inflammation markers (IL-1β, TNF-α, NF-κB p65) and ALT levels post-LPS administration.
  • Supplementation with exogenous AM improved survival and reduced inflammatory responses in AM(+/-) mice.

Conclusions:

  • AM plays a crucial protective role in the liver during LPS-induced endotoxemia.
  • AM is important for regulating systemic inflammation and preventing liver damage.
  • AM deficiency exacerbates endotoxemia-induced liver injury and mortality.

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