Nitric oxide and chronic colitis

  • M. B. Grisham
  • S. Aiko
  • T. E. Zimmerman

Abstract

There is a growing body of both experimental and clinical data to suggest that chronic inflammation of the colon is associated with enhanced production of nitric oxide (NO)1–3. NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect blood flow and leukocyte function4. Furthermore, this reactive nitrogen intermediate will rapidly and spontaneously interact with molecular oxygen or superoxide to yield potentially injurious oxidizing and nitrosating agents. Although the sources of this enhanced NO production in vivo have not been definitively identified, it is very probable that the phagocytic leukocytes (neutrophils, monocytes, macrophages), known to accumulate within the colonic interstitium are primary candidates5. We have demonstrated that extravasated, but not circulating, neutrophils produce much larger amounts of NO via the up-regulation of both mRNA and inducible No synthase (iNOS) enzymatic activity6. Intestinal inflammation induced in experimental animals or in human IBD is associated with increases in one or more tissue-derived cytokines such as tumor necrosis factor (TNF), interferon-γ (IFN-γ) and interleukin-lß (IL-1)7. Some of these cytokines are potent inducers of NO synthase in macrophages, neutrophils and endothelial cells4. In addition we, as well as others, have found that incubation of IL-1, TNF and/or IFN-γ with cultured rat intestinal epithelial cells8,9 for 24 h promotes the release of large quantities of NO 2 and NO 3 . Several groups of investigators have demonstrated that NO produced from activated macrophages is capable of injuring microorganisms, tumor cells and some normal cells such as hepatocytes, pancreatic islet cells and lymphocytes10–4 In view of the potential injurious and proinflammatory properties of NO produced by iNOS, we wished to assess whether NO plays a role in mediating the mucosal injury and inflammation in a model of immunologically induced chronic granulomatous colitis. The objective of this study was to assess the role of NO or NO-derived metabolites as mediators of the mucosal injury and inflammation observed in a model of chronic granulomatous colitis in rats2.

Keywords

Nitric Oxide Inflammatory Bowel Disease Nitric Oxide Mean Arterial Pressure Mucosal Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers and Axcan Pharma, Inc. 1994

Authors and Affiliations

  • M. B. Grisham
  • S. Aiko
  • T. E. Zimmerman

There are no affiliations available

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