INTESTINAL INTERLEUKIN-8 CONCENTRATION AND GENE-EXPRESSION IN INFLAMMATORY BOWEL-DISEASE

Background: Interleukin-8 (IL-8) is an important cytokine for recruitm ent and activation of polymorphonuclear neutrophils (PMNs), cells that are abundant in the intestinal lesions of ulcerative colitis (UC) and Crohn's disease (CD). The present investigation was conducted to eval uate intestinal IL-8 concentration and IL-8 gene expression in paralle l in inflammatory bowel disease (IBD) patients and a non-inflammatory control group. Methods: The intestinal concentration of IL-8 was measu red with a sandwich enzyme-linked immunosorbent assay (ELISA) techniqu e (detection limit, 17.4 pg/mg protein), and relative quantitation of IL-8 mRNA transcript levels was done with a reverse transcription poly merase chain reaction (RT-PCR)-based method. Biopsy specimens from 66 humans who underwent colonoscopy-28 with UC, 18 with CD and colonic in volvement, and 20 non-inflammatory disease-specific controls who subse quently were found to fulfill the diagnostic criteria for irritable bo wel syndrome (IBS)-were included. None had received glucocorticoids wi thin 3 months. Results: Using a one-tailed variance analysis, a signif icant concordance between increasing IL-8 protein concentrations and d isease activity was found both in UC and CD (P < 0.001), and only trac e amounts were detected in IBS biopsy specimens. No differences were f ound between the two groups of UC and CD patients (P > 0.05), and no d ifferences were found between quiescent IBD and IBS (P > 0.05). Howeve r, the PCR method showed IL-8 mRNA in 8 of 18 CD patients (44.4%; 95% confidence limits, 21.5-69.2%) and 7 of 28 UC patients (25.9%; 95% con fidence Limits, 11.1-46.3%), as compared with 0 of 20 IBS (P < 0.005). increased IL-8 mRNA levels were found only in active CD, which was no t the case in UC. No correlation was found between intestinal IL-8 ELI SA and IL-8-mRNA levels (r=0.24, P>0.05). Conclusions: The observed co rrelation between disease activity and expression of the IL-8 gene in active CD colitis but not in UC and the increased IL-8 protein concent rations in affected intestinal segments of IBD as compared with the no ninflamed IBS indicate a possible transient IL-8 gene expression or al tered mRNA stability in UC and CD, as is well known for other cytokine s, such as IL-2. If so, it may form the basis of new therapeutic regim ens for IBD Like IL-10.