Interleukin 16 is up-regulated in Crohn's disease and participates in TNBS colitis in mice.
OBJECTIVE
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.
Keates
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AC
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. akeates@caregroup.harvard.edu
Castagliuolo
I
I
Cruickshank
W W
WW
Qiu
B
B
Arseneau
K O
KO
Brazer
W
W
Kelly
C P
CP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D003106:Colon / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D019410:Interleukin-16 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014302:Trinitrobenzenesulfonic Acid
D000911:Antibodies, Monoclonal; D019410:Interleukin-16; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid