Induction of IL-8 in Inflammatory Bowel Disease

Abstract

Ulcerative colitis (UC) is an inflammatory disease of unknown etiology that is characterized by an influx of inflammatory cells, particularly neutrophils, into the mucosa of the large bowel. Using immunohistochemistry and in situ hybridization, we have previously shown that IL-1 is predominantly expressed by enterocytes in experimental colitis and UC. In a prospective clinical trial, biopsy specimens from 20 consecutive patients with UC and 5 controls, were obtained by endoscopy. IL-8 and IL-1 levels were assessed by ELISA, either in immediately homogenized biopsy specimens or after 23 hour organ culture. Although the diseased bowel mucosa contained more IL-8 than the normal mucosa (200 pg/mg), considerable amounts of IL-8 were also detected in the normal mucosa (98 pg/mg; p=0.004). Moreover, specimens obtained from macroscopically normal and from diseased mucosa from UC patients contained similar amounts of IL-8 (200 vs 180 pg/mg p=0.43). We have shown that, in UC, IL-8 is transcribed and translated by inflammatory cells as well as enterocytes. In HT-29/19a enterocytic cells, IL-8 production can be dose-dependently induced by IL-1 and TNF, and these stimuli are able to induce a stimulus-directed polarized IL-8 secretion that is dependent on rearrangement of the cytoskeleton. In conclusion, large amounts of IL-8 are present in the normal bowel mucosa, suggestive of a role in normal neutrophil and T-cell trafficking. In the diseased bowel, increased levels of IL-8 seem to be important for neutrophil activation in UC, presumably in concert with other stimuli.