RT Journal Article SR Electronic T1 Expression of interleukin 1β and interleukin 1β converting enzyme by intestinal macrophages in health and inflammatory bowel disease JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 214 OP 219 DO 10.1136/gut.42.2.214 VO 42 IS 2 A1 M E McAlindon A1 C J Hawkey A1 Y R Mahida YR 1998 UL http://gut.bmj.com/content/42/2/214.abstract AB Background—In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1β (IL-1β, 31 kD) is processed by IL-1β converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1β is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD). Aims—To investigate the expression and processing of IL-1β and ICE by tissue macrophages from normal and IBD colonic mucosa. Methods—Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay). Results—Normal colonic macrophages synthesised only the precursor form of IL-1β 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 produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1β 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—Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1β, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1β in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.