Nitric oxide in inflammatory bowel disease

The aim of this study was to study nitric oxide (NO) in inflammatory bowel disease (IBD) with a special reference to disease activity and disease location, in bolls an adult and a pediatric patient population, using rectal gas sampling. Furthermore, we investigated the cellular source of the measured NO as well as the relationship between the expression of inducible NO synthase (iNOS) and the proinflammatory TNF-alpha, IL-10 and INF-gamma. Increased NO production was found in active IBD but not inactive disease. Rectal NO levels correlated with disease activity expressed both as clinical activity score and endoscopic inflammatory score in IBD suggesting that rectal NO measurements could be used as an objective quantitative marker of disease activity.

We also showed a subgroup of severely ill IBD patients, not responding to glucocorticosteroid treatment, to have low (< 1000 ppb) initial levels of rectal NO upon onset of flare, suggesting that rectal NO measurements could be used to identify corticosteroid refractory IBD patients, later subjected to colectomy. Increased rectal NO levels were seen in active ulcerative colitis (UC), colorectal Crohn's disease (CD) as well as ileo-cecal CD showing that rectal gas sampling for NO analysis could be used to detect both active ileo-cecal and colorectal disease.

By the correlation between rectal NO levels and mucosal iNOS expression in polymorphonuclear cells in the propria of the colonic mucosa we conclude that the induction of iNOS in these cells plays a major role in the production of the increased luminal NO seen in active IBD. The degree of mucosal iNOS expression displayed significant correlation to the degree of TNF-alpha and IL-1beta but not INF-gamma expression.

To conclude, our present data in IBD specify NO to be a reliable marker of inflammatory activity as indicated by its elaboration by iNOS released from polymorphonuclear leukocytes in the colonic mucosa.

List of scientific papers

I. Herulf M, Ljung T, Hellstrom PM, Weitzberg E, Lundberg JO (1998). Increased luminal nitric oxide in inflammatory bowel disease as shown with a novel minimally invasive method. Scand J Gastroenterol. 33(2): 164-9.
https://pubmed.ncbi.nlm.nih.gov/9517527

II. Ljung T, Herulf M, Beijer E, Jacobsson H, Lundberg J, Finkel Y, Hellstrom PM (2001). Rectal nitric oxide assessment in children with Crohn disease and ulcerative colitis. Indicator of ileocaecal and colorectal affection. Scand J Gastroenterol. 36(10): 1073-6.
https://pubmed.ncbi.nlm.nih.gov/11589381

III. Ljung T, Beijer E, Herulf M, Weitzberg E, Lundberg JO, Finkel Y, Hellstrom PM (2002). Increased rectal nitric oxide in children with active inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 34(3): 302-6.
https://pubmed.ncbi.nlm.nih.gov/11964958

IV. Ljung T, Johansson C, Herulf M, Lundberg JON, Hellstrom PM (2003). Nitric oxide: Luminal marker of inflammation bowel disease. [Manuscript]

V. Ljung T, Axelsson LG, Herulf M, Lundberg JON, Hellstrom PM (2003). Early changes in rectal nitric oxide levels and mucosal inflammatory mediators in Crohns colitis in response to TNF-alpha antibody (infliximab)treatment. [Manuscript]