Network of inflammatory cytokines and correlation with disease activity inulcerative colitis

Objective: The inflammatory component of most human inflammatory chronic di seases implicates the production of proinflammatory cytokines. Tumor necros is factor alpha (TNF alpha) and interleukin 1 beta (IL1 beta) seem to play an important role in ulcerative colitis (UC) in relevant experimental model s. Moreover, antiTNF therapy seems promising experimentally and clinically. However, these cytokines, and TNFa more particularly, are hardly seen in v ivo in such patients. The mediators of choice, correlated with disease acti vities or drug efficacy, remain unclear. To characterize in vivo the networ k of colonic cytokines in patients with UC, and the contribution of the var ious cytokines to disease activity we performed this study, using the colon ic perfusion method. Methods: A 20-cm colon length was perfused. Perfusate samples were collected for cytokine determination by enzyme-linked immnoass ays. Nineteen perfusions were performed in mild to moderate UC, including t wo successive perfusions in four patients. Six healthy control patients and four having Crohn's disease (CD) with rectal involvement were studied. End oscopic score, leukocyte scintigraphy, and systemic markers of inflammation were simultaneously quantified. Results: Large amounts of IL1 beta, TNF al pha, IL6, and IL8 were produced in UC patients with a highly significant co rrelation between TNF alpha, IL1 beta and IL8 two by two. Multivariate fact orial analysis indicated that IL1 beta showed the best correlation with dis ease activity. Locally produced IL6 was strongly associated with circulatin g platelet counts. Moreover, production of inflammatory cytokines was assoc iated with similar variations of disease activity in the four patients with two successive perfusions performed. The level of inflammatory cytokines i n CD was lower than in UC; TNF alpha, IL1 beta, and IL6 were not found in a ny control patients. Conclusion: UC appears to be a chronic inflammatory di sease characterized by high production of all four proinflammatory cytokine s (IL1 beta, TNF alpha, IL6, and IL8). These results suggest that colonic p erfusion may be a suitable method to evaluate the local anticytokine proper ties of new drugs, in correlation with disease activity and systemic marker s of inflammation. (C) 1998 by Am. Coll. of Gastroenterology.