Cyclooxygenase inhibitors enhance tumour necrosis factor production and mortality in murine endotoxic shock

Cytokine. 1994 Sep;6(5):500-3. doi: 10.1016/1043-4666(94)90077-9.

Abstract

Intraperitoneal administration of E. coli lipopolysaccharide (5-15 mg/kg) produced a dose-related increase in mortality which was maximal 72 h after induction of shock. Using a suboptimal dose of LPS (10 mg/kg i.p.), pretreatment with indomethacin (0.1-10 mg/kg p.o) or ibuprofen (1-100 mg/kg p.o) 30 min prior to induction of shock led to a significant enhancement of mortality. This enhancement was associated with a 2-3 fold increase in the peak circulating levels of tumour necrosis factor (TNF-alpha) in the serum of animals treated with indomethacin or ibuprofen compared to vehicle-treated control animals. These results indicate that TNF-alpha production is modulated by endogenous prostaglandins in vivo and that enhanced production of TNF-alpha by cyclooxygenase inhibitors may lead to exacerbation of some inflammatory processes.

MeSH terms

  • Animals
  • Cyclooxygenase Inhibitors / pharmacology*
  • Death
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli
  • Ibuprofen / pharmacology*
  • Indomethacin / pharmacology*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Shock, Septic / immunology*
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Cyclooxygenase Inhibitors
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Ibuprofen
  • Indomethacin