Free radicals and other reactive oxygen metabolites in inflammatory bowel disease: cause, consequence or epiphenomenon?

Oxygen-derived free radicals and other reactive oxygen metabolites have emerged as a common pathway of tissue injury in a wide variety of otherwise disparate disease processes. This has given rise to the hope that efforts directed towards the pharmacologic control of free radical-mediated tissue injury (Reilly, P.M., Schiller, H. J. and Bulkley, G. B. (1991) Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am. J. Surg. 161: 488-503) may have particular application to patients suffering from Crohn's disease and/or ulcerative colitis. However, because tissue injury by any mechanism, even direct mechanical trauma, can elicit an inflammatory response which entails the secondary generation of toxic oxidants by neutrophils and tissue macrophages, it is important that the evidence for this association be examined critically, so as to discriminate the possibility of an etiologic role for these toxic compounds from their presence as a reflection of injury caused primarily by other agents. Similarly, in considering the therapeutic potential of free radical ablation for the treatment of patients with IBD it is important to distinguish between interventions that might specifically block the fundamental injury mechanism from those which would act in a more nonspecific, anti-inflammatory role.