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Am J Physiol Gastrointest Liver Physiol 283: G187-G195, 2002. First published February 27, 2002; doi:10.1152/ajpgi.00331.2001
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Vol. 283, Issue 1, G187-G195, July 2002

Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance

Jun-Ichi Togawa, Hajime Nagase, Katsuaki Tanaka, Masahiko Inamori, Tadashi Umezawa, Atsushi Nakajima, Makoto Naito, Shinobu Sato, Toshifumi Saito, and Hisahiko Sekihara

Third Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama 236-0004, Japan

Natural immunomodulator lactoferrin is known to exert an anti-inflammatory effect. However, there have been no studies that examine the mode of action of lactoferrin in reducing intestinal damage. We investigated the effect of lactoferrin on a trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rats. Bovine lactoferrin was given once daily through gavage, starting 3 days before (preventive mode) or just after TNBS administration (treatment mode) until death. The distal colon was removed to be examined. Colitis was attenuated by lactoferrin via both modes in a dose-dependent manner, as reflected by improvement in macroscopic and histological scores and myeloperoxidase activity. Lactoferrin caused significant induction of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, significant reductions in the proinflammatory cytokines tumor necrosis factor-alpha and IL-1beta , and downregulation of the nuclear factor-kappa B pathway. We concluded that lactoferrin exerts a protective effect against colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.

trinitrobenzenesulfonic acid; inflammatory bowel disease; tumor necrosis factor; interleukin; nuclear factor-kappa B


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