Neutrophils, nitrogen oxides, and inflammatory bowel disease

The etiologic factors responsible for IBD remain only speculative. It does appear that the inappropriate activation of the immune system, whether by immune complex deposition, infectious agents or vascular impairment, is important in the pathogenesis of these diseases. Interaction of certain cytokines known to be produced in human IBD with specific immune cells such as neutrophils and macrophages results in the induction of the enzyme NO. synthase with the concomitant release of large amounts of NO.. Nitric oxide is known to mediate many of the pathophysiological alterations associated with IBD including cell injury, intestinal hyperemia and intestinal smooth muscle dysfunction. In addition, NO. is known to decompose in solution to yield potent N-nitrosating agents which will N-nitrosate certain amines to yield potent carcinogenic nitrosamines. Because antioxidants (including 5-ASA) are potent inhibitors of nitrosamine formation, they may prove useful in attenuating the formation of potentially carcinogenic agents in vivo.