IMBALANCE OF THE INTERLEUKIN-1 SYSTEM IN COLONIC MUCOSA - ASSOCIATIONWITH INTESTINAL INFLAMMATION AND INTERLEUKIN-1 RECEPTOR AGONIST GENOTYPE-2

Background-Interleukin 1 (IL-1) alpha and beta are potent cytokines wh ich play key roles in inflammation. They are controlled by IL-1 recept or antagonist (IL-1ra). Aims-To investigate the influence of mucosal i nflammation and IL-1ra genotype on the IL-1ra:IL-1 balance. Patients a nd methods-IL-1 alpha, IL-1 beta, and IL-1ra were measured by enzyme L inked immunosorbent assay (ELISA) in biopsy specimens taken from infla med and non-inflamed colon of 60 patients with Crohn's disease (CD), 3 4 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non- inflamed controls. IL-1ra genotype was determined by polymerase chain reaction and gel electrophoresis. Results-IL-1 alpha and IL-1 beta wer e significantly increased in inflamed mucosa in inflammatory bowel dis ease (IBD) (CD: 53.5 (22.4) and 409.9 (118.7) pg/mg protein, respectiv ely; UC: 18.9 (6.8) and 214.5 (78.2) pg/mg, respectively) and non-IBD patients (19.2 (7.4) and 281.4 (121.0) pg/mg, respectively; p<0.0001) compared with normal controls (2.8 (0.6) and 30.6 (5.6) pg/mg, respect ively). In CD IL-1 alpha and beta were also significantly increased in non-inflamed mucosa (6.1 (1.3) pg/mg and 88.7 (17.4) pg/mg, respectiv ely; p<0.0012). IL-1ra:(IL-1 alpha+beta) ratios were significantly dec reased in inflamed mucosa of patients with CD (182 (45); p<0.0001), UC (42.5 (136); p=0.0018) and without IBD (221 (76); p<0.0001), and in n on-inflamed mucosa in CD (369 (149); p<0.0001) compared with normal co ntrols (1307 (245); p<0.0001). Patients with IL-1ra genotype 2 had sli ghtly but significantly reduced mucosal IL-1ra concentrations (p=0.003 ). The greatest difference was seen in colonic biopsy specimens from p atients with inflamed Crohn's disease. Conclusion-Mucosal inflammation can modulate the balance of the IL-1:IL-1ra system in colonic mucosa.