Chemiluminescence in inflammatory bowel disease patients: a parameter of inflammatory activity.

BACKGROUND Reactive oxygen species (ROS) are produced in excess in the inflamed mucosa and peripheral blood of patients with inflammatory bowel disease. These species have emerged as a common pathway of tissue injury in a wide variety of inflammatory and other disease processes. The present study was conducted to assess ROS production and to correlate this with parameters of inflammatory activity. METHODS In 25 patients with Crohn's disease (CD), 20 patients with ulcerative colitis (UC) and 65 age- and sex-matched healthy volunteers ROS production was measured using the whole blood luminol enhanced chemiluminescence assay (LECA). Disease activity was assessed using the Crohn's disease activity index and the Ulcerative Colitis Symptoms Score (UCSS) for CD and UC, respectively. Furthermore, the effect of various scavengers, enzymes and enzyme inhibitors on LECA was studied to assess the contribution of different ROS. RESULTS LECA was significantly higher in CD and UC patients compared with healthy controls (7.1+/-4.7 and 9.8+/-6 vs. 5.2+/-2.8 x 10(3) counts per minute (cpm), p<0.05 and <0.001). In CD, relative LECA (patient/control) was correlated with the Crohn's disease activity index and C-reactive protein (CRP) (r=0.54, p=0.001 and r=0.51, p=0.01). In UC, CRP but not LECA was correlated with the Ulcerative Colitis Symptoms Score (C-reactive protein: r=0.42, p=0.01). Addition of azide, superoxide dismutase, deferoxamine and dimethylthiourea resulted in a decrease of LECA values. CONCLUSION Whole blood LECA is increased in patients with CD and UC. This parameter is correlated with disease activity in CD. The observed chemiluminescence is probably due to generation of superoxide and the hydroxyl radical.

[1]  C. Feighery,et al.  Chemiluminescence by polymorphonuclear leucocyte subpopulations in chronic inflammatory bowel disease. Influence of the cell separation procedure. , 1990, Digestion.

[2]  A. Keshavarzian,et al.  Increased production of luminol enhanced chemiluminescence by the inflamed colonic mucosa in patients with ulcerative colitis. , 1993, Gut.

[3]  F Kern,et al.  Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. , 1976, Gastroenterology.

[4]  R. Gugler,et al.  Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylates. Direct evaluation with electron spin resonance spectroscopy. , 1992, Biochemical pharmacology.

[5]  W. Tremaine,et al.  Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. , 1987, The New England journal of medicine.

[6]  H. Verspaget,et al.  Partial defect of neutrophil oxidative metabolism in Crohn's disease. , 1984, Gut.

[7]  J. van Oirschot,et al.  Dimethylthiourea protects rats against gram-negative sepsis and decreases tumor necrosis factor and nuclear factor kappaB activity. , 1997, The Journal of laboratory and clinical medicine.

[8]  G. Mandell,et al.  Chemiluminescence of phagocytic cells. , 1981, Critical reviews in clinical laboratory sciences.

[9]  E. K. Miller,et al.  A demonstration that O2- is a crucial intermediate in the high quantum yield luminescence of luminol. , 1986, Journal of free radicals in biology & medicine.

[10]  F. DeRubertis,et al.  Actions of sulfasalazine and 5-aminosalicylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. , 1987, Gastroenterology.

[11]  J. Lunec,et al.  Free radicals in biological systems--a review orientated to inflammatory processes. , 1987, British medical bulletin.

[12]  R. Allen,et al.  The circulating phagocyte reflects the in vivo state of immune defense , 1992 .

[13]  J. Blanchard,et al.  Potential role of nitric oxide in a model of chronic colitis in rhesus macaques. , 1995, Gastroenterology.

[14]  J. Williams,et al.  Toxic oxygen metabolite production by circulating phagocytic cells in inflammatory bowel disease. , 1990, Gut.

[15]  D. Rampton,et al.  Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease. , 1992, Gastroenterology.

[16]  M. Baker,et al.  Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. , 1996, The Journal of clinical investigation.

[17]  R. B. Fox Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethylthiourea. , 1984, The Journal of clinical investigation.