The observation that lactoferrin can inhibit local inflammation by inhibition of TNF-_ mediated immune responses predicts that lactoferrin exerts a similar antiinflammatory role at local sites of immune defense where the protein is expressed (e.g., the gastrointestinal tract, lung, uterus, etc).

In this regard, the allergen induced cutaneous inflammation model used in the dermal studies described below is mechanistically similar to that observed in Crohn’s disease in humans [74,75], and mimicked by TNBS induced colitis in mice [76,77] both of which are mediated by Th1 cell dependent inflammatory responses.

Consistent with the hypothesis that lactoferrin may play an important role in modulation of gastric inflammation, the protein is expressed in the gastric mucosa of the stomach [78,79] and interacts with receptors localized on gastric intestinal epithelial cells.

Further, the expression of lactoferrin is elevated in the feces of patients with inflammatory conditions including ulcerative colitis and Crohn’s disease [32–34].

Several recent studies carried out in mice have shown that administration of lactoferrin can reduce gastritis induced by Helicobacter felis [80] and protect gut mucosal integrity during lipopolysaccharide-induced endotoxemia [81,82].

While results from human clinical trials to address the efficacy of the protein in regulation of gut inflammatory conditions have not yet been reported, the availability of recombinant human lactoferrin, together with the recently obtained positive results regarding the safety of orally delivered recombinant protein in phase 1 clinical trials [72,83], indicate that efficacy testing is indeed imminent.

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