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. 1996 Feb;38(2):216–222. doi: 10.1136/gut.38.2.216

Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease.

R Daig 1, T Andus 1, E Aschenbrenner 1, W Falk 1, J Schölmerich 1, V Gross 1
PMCID: PMC1383026  PMID: 8801200

Abstract

To test whether there is a difference in the expression of interleukin 8 (IL8) between Crohn's disease and ulcerative colitis and to determine the main site of its synthesis this study analysed IL8 in mucosal biopsy specimens of patients with Crohn's disease and ulcerative colitis by enzyme linked immunosorbent assay (ELISA) and by in situ hybridisation. IL8 was measured by ELISA in 38 normal control patients, eight inflammatory control patients, 55 Crohn's disease biopsy specimens (26 patients), and 67 ulcerative colitis biopsy specimens (35 patients). IL8 mRNA was determined in samples by in situ hybridisation using a specific IL8 RNA probe. IL8 protein was significantly increased in macroscopically inflamed specimens of Crohn's disease (median 118 pg/specimen, p < 0.0001), ulcerative colitis (median 140 pg/specimen, p < 0.001), and inflammatory controls (median 30 pg/specimen, p = 0.010) compared with normal controls (median 4 pg/specimen). IL8 was also increased in uninflamed specimens of Crohn's disease (median 46 pg/specimen, p < 0.001) but not of ulcerative colitis patients (median 9 pg/specimen, p = 0.3). IL8 protein in the mucosa correlated significantly with macroscopic inflammation in Crohn's disease (r = 0.47, p < 0.001) and in ulcerative colitis (r = 0.60, p < 0.001). IL8 mRNA was detected by in situ hybridisation in 31 of 55 biopsy specimens (56%) of Crohn's disease patients, in 38 of 67 specimens of ulcerative colitis patients (57%), in five of eight inflammatory controls (63%) and in five of 38 normal controls (13%). Mucosal IL8 mRNA expression correlated with mucosal IL8 protein (r = 0.46, p < 0.001). IL8 mRNA was only detected in inflammatory cells of the interstitium but not in mucosal epithelial cells. IL8 is produced mainly in the lamina propria of the colon in inflammatory bowel disease and correlates with mucosal inflammation.

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Selected References

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  1. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braegger C. P., Nicholls S., Murch S. H., Stephens S., MacDonald T. T. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet. 1992 Jan 11;339(8785):89–91. doi: 10.1016/0140-6736(92)90999-j. [DOI] [PubMed] [Google Scholar]
  3. Brynskov J., Tvede N., Andersen C. B., Vilien M. Increased concentrations of interleukin 1 beta, interleukin-2, and soluble interleukin-2 receptors in endoscopical mucosal biopsy specimens with active inflammatory bowel disease. Gut. 1992 Jan;33(1):55–58. doi: 10.1136/gut.33.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cappello M., Keshav S., Prince C., Jewell D. P., Gordon S. Detection of mRNAs for macrophage products in inflammatory bowel disease by in situ hybridisation. Gut. 1992 Sep;33(9):1214–1219. doi: 10.1136/gut.33.9.1214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cominelli F., Nast C. C., Clark B. D., Schindler R., Lierena R., Eysselein V. E., Thompson R. C., Dinarello C. A. Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis. J Clin Invest. 1990 Sep;86(3):972–980. doi: 10.1172/JCI114799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cominelli F., Nast C. C., Duchini A., Lee M. Recombinant interleukin-1 receptor antagonist blocks the proinflammatory activity of endogenous interleukin-1 in rabbit immune colitis. Gastroenterology. 1992 Jul;103(1):65–71. doi: 10.1016/0016-5085(92)91096-m. [DOI] [PubMed] [Google Scholar]
  7. Elner V. M., Strieter R. M., Elner S. G., Baggiolini M., Lindley I., Kunkel S. L. Neutrophil chemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells. Am J Pathol. 1990 Apr;136(4):745–750. [PMC free article] [PubMed] [Google Scholar]
  8. Gross V., Andus T., Caesar I., Roth M., Schölmerich J. Evidence for continuous stimulation of interleukin-6 production in Crohn's disease. Gastroenterology. 1992 Feb;102(2):514–519. doi: 10.1016/0016-5085(92)90098-j. [DOI] [PubMed] [Google Scholar]
  9. Gross V., Villiger P. M., Zhang B., Lotz M. Retinoic acid inhibits interleukin-1-induced cytokine synthesis in human monocytes. J Leukoc Biol. 1993 Aug;54(2):125–132. doi: 10.1002/jlb.54.2.125. [DOI] [PubMed] [Google Scholar]
  10. Isaacs K. L., Sartor R. B., Haskill S. Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology. 1992 Nov;103(5):1587–1595. doi: 10.1016/0016-5085(92)91182-4. [DOI] [PubMed] [Google Scholar]
  11. Izzo R. S., Witkon K., Chen A. I., Hadjiyane C., Weinstein M. I., Pellecchia C. Neutrophil-activating peptide (interleukin-8) in colonic mucosa from patients with Crohn's disease. Scand J Gastroenterol. 1993 Apr;28(4):296–300. doi: 10.3109/00365529309090244. [DOI] [PubMed] [Google Scholar]
  12. Mahida Y. R., Kurlac L., Gallagher A., Hawkey C. J. High circulating concentrations of interleukin-6 in active Crohn's disease but not ulcerative colitis. Gut. 1991 Dec;32(12):1531–1534. doi: 10.1136/gut.32.12.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mauch F., Bode G., Ditschuneit H., Malfertheiner P. Demonstration of a phospholipid-rich zone in the human gastric epithelium damaged by Helicobacter pylori. Gastroenterology. 1993 Dec;105(6):1698–1704. doi: 10.1016/0016-5085(93)91065-p. [DOI] [PubMed] [Google Scholar]
  14. Mazzucchelli L., Hauser C., Zgraggen K., Wagner H., Hess M., Laissue J. A., Mueller C. Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. Am J Pathol. 1994 May;144(5):997–1007. [PMC free article] [PubMed] [Google Scholar]
  15. Mitsuyama K., Toyonaga A., Sasaki E., Watanabe K., Tateishi H., Nishiyama T., Saiki T., Ikeda H., Tsuruta O., Tanikawa K. IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1994 Jun;96(3):432–436. doi: 10.1111/j.1365-2249.1994.tb06047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mukaida N., Shiroo M., Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989 Aug 15;143(4):1366–1371. [PubMed] [Google Scholar]
  17. Mullin G. E., Lazenby A. J., Harris M. L., Bayless T. M., James S. P. Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis. Gastroenterology. 1992 May;102(5):1620–1627. doi: 10.1016/0016-5085(92)91722-g. [DOI] [PubMed] [Google Scholar]
  18. Peveri P., Walz A., Dewald B., Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. doi: 10.1084/jem.167.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pullman W. E., Elsbury S., Kobayashi M., Hapel A. J., Doe W. F. Enhanced mucosal cytokine production in inflammatory bowel disease. Gastroenterology. 1992 Feb;102(2):529–537. doi: 10.1016/0016-5085(92)90100-d. [DOI] [PubMed] [Google Scholar]
  20. Schmouder R. L., Strieter R. M., Wiggins R. C., Chensue S. W., Kunkel S. L. In vitro and in vivo interleukin-8 production in human renal cortical epithelia. Kidney Int. 1992 Jan;41(1):191–198. doi: 10.1038/ki.1992.26. [DOI] [PubMed] [Google Scholar]
  21. Schreiber S., Raedler A., Stenson W. F., MacDermott R. P. The role of the mucosal immune system in inflammatory bowel disease. Gastroenterol Clin North Am. 1992 Jun;21(2):451–502. [PubMed] [Google Scholar]
  22. Schröder J. M., Christophers E. Secretion of novel and homologous neutrophil-activating peptides by LPS-stimulated human endothelial cells. J Immunol. 1989 Jan 1;142(1):244–251. [PubMed] [Google Scholar]
  23. Schröder J. M., Mrowietz U., Morita E., Christophers E. Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J Immunol. 1987 Nov 15;139(10):3474–3483. [PubMed] [Google Scholar]
  24. Strieter R. M., Phan S. H., Showell H. J., Remick D. G., Lynch J. P., Genord M., Raiford C., Eskandari M., Marks R. M., Kunkel S. L. Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. J Biol Chem. 1989 Jun 25;264(18):10621–10626. [PubMed] [Google Scholar]
  25. Yoshimura T., Matsushima K., Tanaka S., Robinson E. A., Appella E., Oppenheim J. J., Leonard E. J. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9233–9237. doi: 10.1073/pnas.84.24.9233. [DOI] [PMC free article] [PubMed] [Google Scholar]

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