Mucosal Interleukin-6 Secretion in Ulcerative Colitis: Effects of Anti-Inflammatory Drugs and T-Cell Stimulation

Abstract

Jones SC, Crabtree JE, Rembacken BJ, Dixon MF, Trejdosiewicz LK, Whicher JT, Axon ATR. Mucosal interleukin-6 secretion in ulcerative colitis. Effects of anti-inflammatory drugs and T-cell stimulation. Scand J Gastroenterol 1994;29:722-728.

Background: We have studied modulation of mucosal interleukin-6 (IL-6) secretion by T-cell activation and by anti-inflammatory agents in inflammatory bowel disease. Methods: In vitro secretion of IL-6 by biopsy specimens from patients with active ulcerative colitis was investigated in the presence of cyclosporin-A (CsA) and drugs that have other anti-inflammatory actions. Biopsy specimens from patients with quiescent ulcerative colitis or controls were stimulated with anti-CD3 antibody to activate mucosal T cells. Results: Stimulation of control specimens increased IL-6 secretion (median increase, 147%; p< 0.003), which was prevented by CsA. In quiescent ulcerative colitis there was enhanced spontaneous secretion of IL-6 but a smaller, non-significant increase after T-cell activation (125%). Dexamethasone inhibited secretion in active ulcerative colitis (p < 0.006). 5-Aminosalicylic acid, 6-mercaptopurine, methotrexate, and indomethacin had no effect. There also tended to be a small reduction with CsA, but this just failed to reach statistical significance. Conclusions: In quiescent ulcerative colitis the enhanced spontaneous secretion of IL-6 may be a consequence of mucosal T-cell or macrophage activation: the smaller increase after T-cell stimulation suggests that one or both of these two cell types are already pre-activated.

Key Words:

• Anti-inflammatory agents
• inflammatory bowel disease
• interleukin-6
• T lymphocytes
• ulcerative colitis