Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease

Background: Interleukin-6 (IL-6) has multiple immunological effects on a wi de variety of cells and tissues. The expression of IL-6 and IL-6 receptor ( IL-6R) may be important to the pathogenesis of inflammatory bowel disease ( IBD). Methods: In the present study, we examined whether mucosal IL-6 and soluble IL-6R were associated with the pathophysiology of IBD using the colonic mu cosal specimens obtained from patients with IBD. Enzyme-linked immunosorben t assay was used to measure the levels of IL-6 and sIL-6R in organ cultures of mucosal tissues and in cell cultures of fractionated mucosal cells as w ell as in the serum. Expression of IL-6 and IL-6R was analysed by reverse t ranscription-polymerase chain reaction analysis using freshly isolated lami na propria mononuclear cells (LPMC). Results: The levels of IL-6 and sIL-6R in organ cultures were substantially elevated in patients with IBD, especially in those with histologically act ive inflammation. In contrast, considerably higher levels of sIL-6R were de tected in patients with other types of colonic inflammation who were includ ed as inflammatory controls, but elevation of IL-6 was less prominent in su ch patients. The positivity for expression of IL-6 and IL-6R mRNA in LPMC w as in parallel with the results obtained in organ cultures. In cell culture s, mucosal macrophages were the main cell type producing both IL-6 and sIL- 6R on a per cell basis and other cell fractions including colonic epithelia l cells and lymphocytes produced substantially lower amounts of these molec ules. The levels of IL-6 and sIL-6R in organ cultures, but not those in the serum, showed a significantly positive correlation with the degree of clin ical disease activity in patients with IBD. Conclusions: Enhanced IL-6/sIL-6R-mediated immune and inflammatory response s may be implicated, at least partly, in the continuation of intestinal inf lammation in patients with IBD. (C) 1999 Blackwell Science Asia Pty Ltd.