Pretreatment with ibuprofen augments circulating tumor necrosis factor-alpha, interleukin-6, and elastase during acute endotoxinemia

J Infect Dis. 1991 Jan;163(1):89-95. doi: 10.1093/infdis/163.1.89.

Abstract

Plasma levels of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were monitored after intravenous administration of Escherichia coli endotoxin with or without ibuprofen pretreatment to healthy volunteers. Intravenous endotoxin (n = 7) resulted in elevated plasma TNF alpha concentrations with maximal levels at 90 min (369 +/- 44 pg/ml, P less than .001 vs. saline controls, n = 7). The rise in TNF-alpha was followed by a rise in plasma IL-6 (27 +/- 12.8 ng/ml), peaking 30-90 min thereafter. Pretreatment with ibuprofen (n = 6) caused a significant augmentation and temporal shift in cytokine elaboration with maximal TNF alpha levels (627 +/- 136 pg/ml) at 120 min and IL-6 peaks (113 +/- 66 ng/ml) at 180 min. In ibuprofen-treated volunteers, the additional increase in TNF alpha was paralleled by increased levels of circulating elastase. In vitro experiments suggest a causal relationship between these events. Thus, the cyclooxygenase inhibitor ibuprofen blunts the clinical response to endotoxin but augments circulating cytokine levels and leukocyte degranulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Pressure
  • Body Temperature
  • Cell Degranulation
  • Endotoxins / blood*
  • Escherichia coli
  • Heart Rate
  • Humans
  • Ibuprofen / therapeutic use*
  • Interleukin-1 / blood
  • Interleukin-6 / blood*
  • Least-Squares Analysis
  • Leukocyte Count
  • Male
  • Neutrophils / enzymology
  • Neutrophils / physiology
  • Pancreatic Elastase / blood*
  • Regression Analysis
  • Tumor Necrosis Factor-alpha / analysis*

Substances

  • Endotoxins
  • Interleukin-1
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Pancreatic Elastase
  • Ibuprofen