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Abstract

The hypothesis that lactoferrin protects mice against lethal effects of bacterial lipopolysaccharide (LPS) is the subject of experimental investigations described in this article. Lipopolysaccharide is a powerful toxin produced by gram negative bacteria that when injected into humans or experimental animals reproduce many of the pathophysiologic and immune responses caused by live bacteria. Lactoferrin administered intraperitoneally 1 hr prior to injection of LPS significantly enhanced the survival of mice, reducing LPS-induced mortality from 83.3% to 16.7%. Changes in locomotor and other behavioral activities resulting from LPS injection were not present in mice treated with lactoferrin. Also, histological examination of intestine revealed remarkable resistance to injury produced by LPS if mice were pretreated with lactoferrin. Severe villus atrophy, edema and epithelial vacuolation were observed in LPS-treated animals but not in lactoferrin-treated counterparts. Electrophysiological parameters were used to assess secretory and absorptive functions in the small intestine. In mice treated with LPS, transmural electrical resistance was reduced and absorption of glucose was increased. Lactoferrin treatment had no significant influence on basal electrophysiological correlates of net ion secretion or glucose absorption nor on changes induced by LPS. Collectively, these results suggest that lactoferrin attenuates the lethal effect of LPS and modulates behavioral and histopathological sequela of endotoxemia.

Oral Administration of Lactoferrin Attenuates Intestinal Ischemia-Reperfusion Injury in Rats

“…In addition, the endotoxemia induced by intestinal I/R also contributes to gut damage as SMA occlusion causes intestinal ischemia, stasis and damage to the intestinal barriers, resulting in release of endotoxin into intestinal tissues following reperfusion. It has been reported that preoperative administration of Lf protected gut mucosal integrity during endotoxemia induced by LPS [10], and attenuated the increased diarrheogenic activity, gastrointestinal transit and production of NO and PGE 2 induced by LPS [7]. These results indicate that Lf could ameliorate I/R-induced gut injury by inhibiting the release of proinflammatory cytokines, neutrophil infiltration and protecting gut epithelial cells from endotoxemia.…”

“…Several biological functions have been attributed to Lf, including iron absorption in the intestine, promoting intestinal cell growth, protecting the host from microbial infection, enhancing intestinal mucosal immunity, and regulating myelopoiesis and systemic immune response [7]. It has been reported that oral administration of Lf reduced methotrexate-induced small intestine damage [8], lipopolysaccharide (LPS)-induced diarrhea [9,] gut damage [10] and colitis [11]. Lf also showed antioxidative activities against hydrogen peroxide-induced oxidative damage in intestinal epithelial cells [12].…”

Immunomodulatory effects of recombinant lactoferrin during MRSA infection

“…Both the rmLF and rhLF demonstrated a decrease in inflammatory cytokine production from monocytes and increased cytokine production from granulocytes during MRSA infection, indicating that autologous LF effects share many activities between species. The in vivo mouse model showed that treatment with rmLF decreased circulating IL-6 with 100µg/mouse dose, which represents a dose considerably lower compared to previously published reports using the bovine LF (20, 32, 42–44). This decrease in serum IL-6 is theoretically important for host survival in the mouse sepsis model, as high levels of IL-6 in the early sepsis phase may be a predictor of mortality (45).…”

“…In humans, several investigators have now reported that oral bovine LF is effective as a prophylactic to prevent onset of sepsis in high risk infants (36–39). Bovine LF has been shown to protect gut integrity in mouse models of LPS endotoxemia (32) or gram negative bacteremia (40). However, the conclusion of these studies suggests a mechanism tied to protection of gut integrity to prevent translocation of intestinal-residing bacteria, rather than straight improvement due to decreased bacterial load or modification of cytokine storm post infection.…”

Evaluation of the protective effect of bovine lactoferrin against lipopolysaccharides in a bovine mammary epithelial cell line

“…Several studies have documented the protective effect of Lf against endotoxinmediated damage. Hirotani et al (2008) have reported the defensive role of Lf against LPSmediated intestinal mucosal damage in human intestinal epithelial Caco-2 cell line and in vivo studies have provided evidence that orally administered bLf has a beneficial effect against a lethal dose of LPS, thus preventing septic shock (Lee et al 1998;Kruzel et al 2000). Tian et al (2010) have reported the cytoprotective effect of bLf against endotoxin LPS in both immune cells and colon epithelial cells.…”