title: Production and cellular source of interleukin-8 in ulcerative colitis.
abstract: : Evidence has accumulated that interleukin-1β (IL-1β) plays an pivotal role in mediating the inflammatory changes in ulcerative colitis (UC) and that interleukin-8 (IL-8) is responsible for some of the neutrophil-activating actions of IL-1β in vivo. We determined the IL-8 content and its cellular source in mucosal specimens of patients with UC, and analyzed whole gut lavage fluid on the presence of IL-8. In addition, we monitored these patients for a follow-up period of 1 year to see if IL-8 levels are indicative for colon at risk. Patients with active disease were enrolled; disease activity, endoscopical scores, and histopathological grading were assessed. Transcription and translation of IL-8 were demonstrated by in situ hybridisation and immunohistochemistry. Biopsy specimens from 30 UC patients and five controls were homogenized, and IL-8 content was determined. Lavage fluid from 10 UC patients and six controls was processed and analyzed for the presence of IL-8. Clinical events were monitored for a period of 1 year. IL-8 production was detected in both enterocytes and mucosal inflammatory cells. The mean IL-8 content in control biopsy specimens was 98.0 pg/mg (±10 pg/mg). The IL-8 content was 176.7 pg/mg (±21 pg/mg) in specimens obtained from noninflamed colon regions of UC patients, and 204 pg/mg (±27 pg/mg) in specimens taken from inflamed colonic areas (p = 0.023 and p = 0.013, respectively). The mean IL-8 levels in lavage fluid from UC patients was 36.4 pg/ml (±22.5 pg/ml) versus 3.1 pg/ml (±0.8 pg/ml) in control patients (p < 0.05). Lavage IL-8 levels correlated with endoscopical score (r = 0.81; p = 0.009). During a follow-up period of 1 year, patients with high IL-8 levels in their noninvolved colon mucosa experienced more flare-ups than patients with low levels of normal mucosal IL-8. This study demonstrates that IL-8 is expressed in the normal large bowel mucosa. High levels are present in both macroscopically inflamed and noninflamed mucosa in UC. Both enterocytes and inflammatory cells contribute to the IL-8 production. Analysis of gut perfusate can be used to study IL-8 in UC, and IL-8 production in normally appearing mucosa in patients with ulcerative colitis may be indicative of colon at risk for inflammation.
authors.affiliation: *Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, and †Department of Gastroenterology, Academic Medical Center, University of Amsterdam, The Netherlands; and ‡Sandoz Forchungsinstitut, Vienna, Austria.
authors.forename: D W
authors.initials: DW
authors.lastname: Hommes
authors.forename: S A
authors.initials: SA
authors.lastname: Radema
authors.forename: J
authors.initials: J
authors.lastname: Jansen
authors.forename: F
authors.initials: F
authors.lastname: Smit
authors.forename: P
authors.initials: P
authors.lastname: Fockens
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Ceska
authors.forename: G N
authors.initials: GN
authors.lastname: Tytgat
authors.forename: S J
authors.initials: SJ
authors.lastname: van Deventer