Immunopathology of NSAID-gastropathy: inhibitory effects of interleukin-I and cyclosporin A

Ann N Y Acad Sci. 1992:664:400-7. doi: 10.1111/j.1749-6632.1992.tb39778.x.

Abstract

The present study demonstrates that CSA is capable of inhibiting indomethacin-induced leukocyte adherence to the vascular endothelium, and can reduce the severity of indomethacin-induced gastric mucosal injury. These results are therefore consistent with the hypothesis that leukocyte (particularly neutrophil) adherence is a critical event in the pathogenesis of NSAID-induced gastropathy. The mechanism through which CSA inhibits leukocyte adherence is not clear, and warrants further investigation. This study also confirmed the protective effects of IL-1 in experimental NSAID-gastropathy, and demonstrates that one of the ways the IL-1 may protect the mucosa is through its ability to inhibit the release of proinflammatory mediators (e.g., PAF) and promote the release of antiinflammatory mediators (e.g., nitric oxide). IL-1 modulated the release of these mediators from peritoneal mast cells at doses in the pg/ml to ng/ml range. IL-1 can inhibit the ability of neutrophils to respond to chemotactic stimuli and can prevent LTB4-induced neutropenia. Inhibition of neutrophil function by IL-1 may therefore account for its ability to reduce NSAID-induced gastric mucosal injury. Whether or not effects of IL-1 on the production of mediators such as nitric oxide and PAF is an underlying mechanism for the inhibitory effects on neutrophil function remains to be determined.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Cell Adhesion / drug effects*
  • Cyclosporine / pharmacology*
  • Gastric Mucosa / drug effects
  • Humans
  • Interleukin-1 / pharmacology*
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Stomach Ulcer / immunology*
  • Stomach Ulcer / prevention & control

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1
  • Cyclosporine