EXPRESSION OF INTERLEUKIN-1-BETA AND INTERLEUKIN-1-BETA CONVERTING-ENZYME BY INTESTINAL MACROPHAGES IN HEALTH AND INFLAMMATORY BOWEL-DISEASE

Background-In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1 beta (IL-1 beta, 31 kD) is processed by IL-1 beta converting enzyme (ICE) to the mature, bioa ctive form (17 kD). IL-1 beta is a proinflammatory cytokine which is l ikely to have a role in the pathogenesis of inflammatory bowel disease (IBD). Aims-To investigate the expression and processing of IL-1 beta and ICE by tissue macrophages from normal and IBD colonic mucosa. Met hods-Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain rea ction (RT-PCR), western blot analysis, and ELISA (enzyme linked immuno sorbent assay). Results-Normal colonic macrophages synthesised only th e precursor form of IL-1 beta whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produ ced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldeh yde Inhibitor of ICE, significantly reduced the amount of mature IL-1 beta released by isolated IBD macrophages (from a median of 1.2 (range 0.78-4.42) ng/ml to 0.43 (0.21-1.6) ng/ml; p<0.01). Conclusions-Expos ure of normal colonic macrophages to EPS only induces the production o f the precursor form of IL-1 beta, because the cells fail to activate ICE. In contrast, IL-1 beta colonic macrophages are able to activate I CE and hence release mature IL-1 beta in a manner similar to circulati ng monocytes. This is consistent with PBD macrophages being recently r ecruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.