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Am J Physiol Gastrointest Liver Physiol (February 27, 2002). doi:10.1152/ajpgi.00331.2001
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Articles in PresS, published online ahead of print February 27, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00331.2001
Submitted on July 26, 2001
Accepted on February 20, 2002

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

Jun-ichi Togawa1*, Hajime Nagase1, Katsuaki Tanaka1, Masahiko Inamori1, Tadashi Umezawa1, Atsushi Nakajima1, Makoto Naito1, Shinobu Sato1, Toshifumi Saito1, and Hisahiko Sekihara1

1 The Third Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan

* To whom correspondence should be addressed. E-mail: j-togawa{at}qb3.so-net.ne.jp.

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 trinitrobenzene sulfonic acid (TNBS) induced-colitis in rats. Bovine lactoferrin was given once daily through gavage, starting three days before (preventive mode) or just after TNBS-administration (treatment mode) until sacrifice. 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. Significant induction of the anti-inflammatory cytokines, interleukin-4 and interleukin-10, and significant reductions in the proinflammatory cytokines, tumor necrosis factor {alpha} and interleukin-1ß, accompanied by down-regulation of the nuclear factor {kappa}B pathway, by lactoferrin administered were also observed. 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.




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