Abstract

Whole gut lavage is currently used in children as preparation-before radiological or endoscopic examination of the large bowel. The fluid obtained is a gut perfusate, and in adults has been recently used to measure intestinal immunity and inflammation. In this work proinflammatory cytokines (IL1, IL6, IL8, TNFα), interleukin 1 receptor antagonist (IL1ra) and IL1ra/IL1 ratio have been measured in the whole gut lavage fluid (WGLF) obtained from children with inflammatory bowel disease (IBD). The gut lavage procedure has been performed in 24 patients affected by Crohn's disease (CD) (median age 9.9 years, range 3.2-17.9) and 17 affected by ulcerative colitis (UC) (median age 9.6 years, range 2.1-17.5); 23 age-matched disease-controls were also investigated Isotonic, non absorbable polyethylenglicole-based lavage solution was given at a rate of 30 ml/Kg/hour. When clear fluid was passed, samples were collected, filtered and treated with protease inhibitors. Sandwich ELISA techniques were used for measurement of IgG, IL1β, IL-1ra, TNFα, IL6 and IL8. Both in UC (mean; 95% CI:91.2; 48.5-17.6 pg/ml) and in CD (35.5; 18.9-66.7) patients, WGLF IL1β levels were significantly (p<0.001) higher than in controls (9.8; 5.4-17.6). A statistically significant (p<0.001) correlation was found between IL1β and intestinal IgG levels, known to be reliable index of disease activity. IL1ra levels were similar in CD (3,236; 2,156-4,857 pg/ml) when compared to controls (3,890; 2,264-6,687), but higher in UC (7,762; 5,660-10,646). The IL1ra/IL1β ratio was significantly (p<0.02) lower both in UC and CD patients, and negatively (p<0.001) correlated with IgG WGLF levels. High levels of IL8 were found only in 4 patients affected by active CD and in 4 affected by active UC, never in controls. In no case TNFα and IL6 could be measured in WGLF. In conclusion, high concentrations of IgG and IL1β have been measured in the gut lavage fluid from children with active IBD. An imbalance of the IL1ra/IL1β ratio has also been observed: its relevance to the pathogenesis of IBD awaits further study.

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