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

Gastroenterology. 2000 Oct;119(4):972-82. doi: 10.1053/gast.2000.18164.

Abstract

Background & 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 polymerase 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-1beta (P<0.05) and tumor necrosis factor alpha (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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Colitis / chemically induced
  • Colitis / genetics*
  • Colitis / immunology
  • Colitis / therapy
  • Colon / immunology*
  • Colon / pathology
  • Crohn Disease / genetics*
  • Crohn Disease / immunology
  • Crohn Disease / pathology
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Humans
  • Interleukin-16 / analysis
  • Interleukin-16 / genetics*
  • Interleukin-16 / immunology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*
  • Trinitrobenzenesulfonic Acid

Substances

  • Antibodies, Monoclonal
  • Interleukin-16
  • RNA, Messenger
  • Trinitrobenzenesulfonic Acid