Interleukin 16 is up-regulated in Crohn’s disease and participates in TNBS colitis in mice

Abstract

Backround and Aims: Interleukin (IL)-16 is a T lymphocyte-derived cytokine that uses CD4 as its receptor and hence selectively recruits CD4-bearing cells. Infiltrating CD4+ T cells are a feature of Crohn’s disease; however, the role of IL-16 in intestinal inflammation is unknown. The aim of this study was to determine whether IL-16 production is increased in inflammatory bowel disease and whether IL-16 participates in trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods: IL-16 messenger RNA and protein levels in inflammatory bowel disease tissues were determined by reverse-transcription polyrnerase chain reaction and enzyme-linked immunosorbent assay. C57BL/6 or BALB/c mice were treated with vehicle, TNBS alone, TNBS + anti-IL-16 monoclonal antibody (mAb), TNBS + control mAb, or were untreated. Colonic injury and inflammation were evaluated after 3 or 10 days. Results: Colonic IL-16 protein levels were increased in patients with Crohn’s disease (P < 0.05) but not ulcerative colitis. Anti-IL-16 mAb treatment significantly reduced TNBS-induced weight loss (P < 0.001), mucosal ulceration (P < 0.05), myeloperoxidase activity (P < 0.001), and TNBS-mediated increases in mucosal levels of IL-1β (P < 0.05) and tumor necrosis factor α (P < 0.01). Conclusions: Anti-IL-16 mAb reduced colonic injury and inflammation induced by TNBS in mice. Colonic mucosal IL-16 levels were elevated in Crohn’s disease, suggesting a role for IL-16 in the pathophysiology of inflammatory bowel disease.