Skip to main content
SpringerLink
Log in

Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis

  • Intestinal Disorders, Inflammatory Bowel Disease, Immunology, And Microbiology
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P<0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R)α andβ chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (<1.0 pg/ml) (P<0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r=0.46;P<0.0001), and between sICAM-1 and sIL-2Rα concentrations (r=0.69;P<0.0001), while sIL-2Rβ was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2Rα levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gearing AJH, Newman W: Circulating adhesion molecules in disease. Immunol Today 14:506–512, 1993

    PubMed  Google Scholar 

  2. Pedersen G, Brynskov J, Nielsen OH, Bendtzen K: Adhesion molecules in inflammatory and neoplastic intestinal diseases. Dig Dis 13:322–336, 1995

    PubMed  Google Scholar 

  3. Brynskov J, Nielsen OH, Ahnfelt-Rønne I, Bendtzen K: Cytokines and their natural regulation in inflammatory bowel disease: A review. Dig Dis 12:290–304, 1994

    PubMed  Google Scholar 

  4. Merluzzi VJ, Rothlein R, Wood C, Stearns CD, Faanes RB, Last-Barney K: Inhibition of human mixed lymphocytes reactions by monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1).In Leukocyte Adhesion Molecules. TA Springer, DC Anderson, AS Rosenthal, R Rothlein (eds). New York, Springer-Verlag, 1989, pp 244–251

    Google Scholar 

  5. Nielsen OH:In vitro studies on the significance of arachidonate metabolism and other oxidative processes in the inflammatory response of human neutrophils and macrophages with special reference to inflammatory bowel disease. Scand J Gastroenterol 23(suppl 150):1–21, 1988

    PubMed  Google Scholar 

  6. Brynskov J: Cyclosporin in Crohn's disease. Therapeutic and pathogenetic implications. Dan Med Bull 41:332–344, 1994

    PubMed  Google Scholar 

  7. Nielsen OH, Langholz E, Hendel J, Brynskov J: Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in active inflammatory bowel disease. Dig Dis Sci 39:1918–1923, 1994

    PubMed  Google Scholar 

  8. Nielsen OH, Brynskov J: Soluble interleukin-2 receptors in ulcerative colitis. Mediat Inflamm 2:115–118, 1993

    Google Scholar 

  9. Gorski A: The role of cell adhesion molecules in immunopathology. Immunol Today 15:251–255, 1994

    PubMed  Google Scholar 

  10. Raab Y, Gerdin B, Ahlstedt S, Hällgren R: Neutrophil mucosal involvement is accompanied by enhanced local production of interleukin-8 in ulcerative colitis. Gut 34:1203–1206, 1993

    PubMed  Google Scholar 

  11. Kirman I, Nielsen OH, Kjaersgaard E, Brynskov J: Interleukin-2 receptor α and β chain expression by circulating αβ and γδ T cells in inflammatory bowel disease. Dig Dis Sci 40:291–295, 1995

    PubMed  Google Scholar 

  12. Langholz E, Munkholm P, Nielsen OH, Kreiner S, Binder V: Incidence and prevalence of ulcerative colitis in Copenhagen county from 1962 to 1987. Scand J Gastroenterol 26:1247–1256, 1991

    PubMed  Google Scholar 

  13. Langholz E, Munkholm P, Davidsen M, Binder V: Course of ulcerative colitis: Analysis of changes in disease activity over years. Gastroenterology 107:3–11, 1994

    PubMed  Google Scholar 

  14. Søltoft J, Gudmand-Høyer E, Krag E, Kristensen E, Wulff HR: A double-blind trial of the effect of wheat bran on symptoms of irritable bowel syndrome. Lancet 1:270–271, 1976

    PubMed  Google Scholar 

  15. Binder V: A comparison between clinical state, macroscopic and microscopic appearances of rectal mucosa, and cytologic picture of mucosal exudate in ulcerative colitis. Scand J Gastroenterol 5:627–632, 1970

    PubMed  Google Scholar 

  16. Vainer B, Nielsen OH: Serum concentration and chemotactic activity of E-selectin (CD62E) in inflammatory bowel disease. Mediat Inflamm 3:215–218, 1994

    Google Scholar 

  17. Nielsen OH, Prifti SK, Peichl P, Lindley I, Scheibel J, Horn T: Influence ofHelicobacter pylori on gastric mucosal interleukin-8 synthesis: A Danish-Albanian collaborative study. Scand J Gastroenterol Hepatol 1996 (submitted)

  18. Pigot R, Dillon LP, Hemmingway LH, Gearing AJH: Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 187:584–589, 1992

    PubMed  Google Scholar 

  19. Malizia G, Calabrese A, Cottone M, Raimondo M, Trejdosiewicz LK, Smart CJ, Oliva L, Pagliaro L: Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. Gastroenterology 100:150–159, 1991

    PubMed  Google Scholar 

  20. Nakamura S, Ohtani H, Watanabe Y, Fukushima K, Matsumoto T, Kitano A, Kobayashi K, Nagura H:In situ expression of the cell adhesion molecules in inflammatory bowel disease: Evidence of immunologic activation of vascular endothelial cells. Lab Invest 69:77–85, 1993

    PubMed  Google Scholar 

  21. Rothlein R, Mainolfi EA, Czajkowski M, Marlin SD: A form of circulating ICAM-1 in human serum. J Immunol 147:3788–3793, 1991

    PubMed  Google Scholar 

  22. 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 96:432–436, 1994

    PubMed  Google Scholar 

  23. Koizumi M, King N, Lobb R, Benjamin C, Podolsky DK: Expression of vascular adhesion molecules in inflammatory bowel disease. Gastroenterology 103:840–847, 1992

    PubMed  Google Scholar 

  24. Cybulsky MI, Fries JWU, Williams AJ, Sultan P, Davis VM, Gimbrone MA Jr, Collins T: Alternative slicing of human VCAM-1 in activated vascular endothelium. Am J Pathol 138:815–820, 1991

    PubMed  Google Scholar 

  25. Podolsky DK, Lobb R, King N, Benjamin CD, Pepsky B, Sengal P, de Beaumont M: Attenuation of colitis in the cotton-top tamarin by anti-α4 integrin monoclonal antibody. J Clin Invest 92:372–380, 1993

    PubMed  Google Scholar 

  26. Goggins MG, Mahmud N, McDonald GS, Weir DG, Kelleher D: Serum VCAM-1 reflects the grade of intestinal inflammation in patients with Crohn's disease. Gastroenterology 108(suppl):A825, 1995

    Google Scholar 

  27. Ohtani H, Nakamura S, Watanabe Y, Fukushima K, Mizoi T, Kimura M, Hiwatashi N, Nagura H: Light and electron microscopic immunolocalization of endothelial leucocyte adhesion molecule-1 in inflammatory bowel disease. Morphological evidence of active synthesis and secretion into vascular lumen. Virchows Arch A Pathol Anat Histopathol 420:403–409, 1992

    PubMed  Google Scholar 

  28. Raud J, Lindbom L: Leukocyte rolling and firm adhesion in the microcirculation. Gastroenterology 104:310–323, 1993

    PubMed  Google Scholar 

  29. Grabstein KH, Eisenman J, Shanebeck K, Rauch C, Srinivasan S, Fung V, Beers C, Richardson J, Schoenborn MA, Ahdieh M, Johnson L, Alderson MR, Watson JD, Anderson DM, Giri JG: Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor. Science 264:965–968, 1994

    PubMed  Google Scholar 

  30. Crabtree JE, Juby LD, Heatley RV, Lobo AJ, Bullimore DW, Axon ATR: Soluble interleukin-2 receptor in Crohn's disease: Relation of serum concentrations to disease activity. Gut 31:1033–1036, 1990

    PubMed  Google Scholar 

  31. Mahida YR, Gallagher A, Kurlak L, Hawkey CJ: Plasma and tissue interleukin-2 receptor levels in inflammatory bowel disease. Clin Exp Immunol 82:75–80, 1990

    PubMed  Google Scholar 

  32. Matsuura T, West GA, Klein JS, Ferraris L, Fiocchi C: Soluble interleukin 2 and CD8 and CD4 receptors in inflammatory bowel disease. Gastroenterology 102:2006–2014, 1992

    PubMed  Google Scholar 

  33. Chiu G, Rajapakse CN: Cutaneous polyarteritis nodosa and ulcerative colitis. J Rheumatol 18:769–770, 1991

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

    O. H. Nielsen MD, DMSc, J. Brynskov MD, DMSc & B. Vainer MD

  2. Department of Gastroenterology F, Glostrup Hospital, University of Copenhagen, Ndr. Ringvej, DK-2600, Glostrup, Denmark

    O. H. Nielsen MD, DMSc, J. Brynskov MD, DMSc & B. Vainer MD

Authors
  1. O. H. Nielsen MD, DMSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Brynskov MD, DMSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Vainer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study was kindly supported by grants from Executive Jacob Madsen's and spouse Olga Madsen's Foundation and the Else and Mogens Wedell-Wedellsborg's Foundation.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nielsen, O.H., Brynskov, J. & Vainer, B. Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis. Digest Dis Sci 41, 1780–1785 (1996). https://doi.org/10.1007/BF02088745

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02088745

Key words

Search

Navigation