INCREASED MUCOSAL CONCENTRATIONS OF SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 (SICAM-1), SE-SELECTIN, AND INTERLEUKIN-8 IN ACTIVE ULCERATIVE-COLITIS

Cell surface adhesion molecules (CAM) are important promoters of the i mmunoinflammatory cascade, The circulating levels of soluble intercell ular adhesion molecule 1 (ICAM-1) have previously been shown to correl ate with disease activity in inflammatory bowel disease, The primary a im 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 pati ents with ulcerative colitis (UC) and 14 controls and found that the m edian concentration of soluble ICAM-1 was significantly higher in pati ents with, moderately or very active UC (15.0 ng/ml) as compared to sl ightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as contr ols (6.5 ng/ml) (P < 0.005), To further elucidate the interactions, tw o other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCA M-1)], together with interleukin-8 (TL-S), IL-2 receptor (IL-2R) alpha and beta chains, were also measured, A significant trend towards high er 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, Ln contrast, soluble VCAM-1 was barely detectab le in biopsies from two UC patients, A significant correlation was fou nd between soluble ICAM-1 and IL-S concentrations (r = 0.46; P < 0.000 1), and between sICAM-1 and sIL-2R alpha concentrations (r = 0.69. P < 0.0001), while sIL-2R beta was not detected. This study shows that in testinal ICAM-1 and E-selectin correlate with endoscopic activity of U C and with IL-8 and IL-2R alpha levels, These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeuti cal potential of targeting CAM, The lack of detectable VCAM-1, which i s induced only in venous endothelium is interesting. It may suggest th at intestinal inflammation mainly affects arterial endothelial cells a nd support the theory that intestinal vasculitis is involved in the pa thogenesis of inflammatory bowel disease.