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Granisetron protects polymicrobial sepsis-induced acute lung injury in mice

Jun Wang1, Shenhai Gong2, Fangzhao Wang2

  • 1Department of Respiration, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.

Biochemical and Biophysical Research Communications
|December 16, 2018
PubMed

Insights

Granisetron, an anti-nausea drug, shows promise in treating sepsis-induced acute lung injury (ALI). It reduces lung damage and inflammation by inhibiting key inflammatory pathways.

Area of Science:

  • Immunology
  • Pharmacology
  • Critical Care Medicine

Background:

  • Sepsis is a life-threatening condition with significant global mortality.
  • Sepsis-induced acute lung injury (ALI) is a severe complication.
  • Granisetron is primarily used as an anti-nausea medication.

Purpose of the Study:

  • To investigate the potential therapeutic effects of granisetron on sepsis-induced ALI.
  • To elucidate the underlying mechanisms by which granisetron may impact ALI.

Main Methods:

  • Animal models of sepsis-induced ALI were treated with granisetron.
  • Macrophage cell lines (THP-1) were stimulated with lipopolysaccharide (LPS) in vitro.
  • Pulmonary neutrophil recruitment, chemokine expression (Cxcl1, Cxcl2), and inflammatory signaling pathways (p38 MAPK, NLRP3 inflammasome) were assessed.

Main Results:

  • Granisetron treatment significantly reduced lung damage in mice with sepsis-induced ALI.
  • Administration of granisetron decreased neutrophil infiltration in the lungs.
  • Granisetron suppressed Cxcl1 and Cxcl2 expression in macrophages and inhibited p38 MAPK and NLRP3 inflammasome activation.

Conclusions:

  • Granisetron demonstrates a protective effect against sepsis-induced ALI.
  • The mechanism involves the suppression of macrophage chemokine production (Cxcl1/Cxcl2) and reduced neutrophil recruitment.
  • Granisetron's anti-inflammatory properties extend beyond its anti-nausea effects, offering potential for ALI treatment.
Keywords:
ALICxcl1/Cxcl2GranisetronNeutrophilNlrp3 inflammasomeSepsis

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