Human Lactoferrin and Peptides Derived from a Surface-Exposed Helical Region Reduce ExperimentalEscherichia coliUrinary Tract Infection in Mice

Abstract

Escherichia coli bacteria into the urinary bladder. The control groups received phosphate-buffered saline or water. C3H/Tif mice were treated with hLF or bLF, and C3H/HeN mice were treated with bLF only. The numbers of bacteria in the kidneys and bladder of C3H/Tif and C3H/HeN mice were significantly reduced 24 h later by the LF treatments compared to the findings for the control group. The hLF-treated group showed the strongest reduction compared with the vehicle-treated-group (P values were 0.009 and 0.0001 for the kidneys and bladder, respectively). The urinary leukocyte response was diminished in the hLF-treated group. The hLF treatment also significantly reduced the urinary interleukin-6 (IL-6) levels at 2 h and the systemic IL-6 levels at 24 h after infection (P values were 0.04 and < 0.002, respectively). In the bLF-treated animals, no such strong antiinflammatory effects were obtained. In another series of experiments, C3H/Tif mice perorally treated with HLD1 or HLD2 also showed reduced numbers of bacteria in the kidneys compared with the vehicle-treated mice, although the results were significantly different only for HLD2 (P < 0.01). Analysis of urine from hLF-fed C3H/ Tif mice showed that hLF was excreted into the urinary tract at 2 h after feeding. Testing of the in vitro bactericidal activity of LF (1 mg/ml) or the peptides (0.1 mg/ml) in mouse urine against the E. coli bacteria revealed moderate killing only by HLD2. In conclusion, these results demonstrate for the first time that oral administration of hLF or peptides thereof is effective in reducing infection and inflammation at a remote site, the urinary tract, possibly through transfer of hLF or its peptides to the site of infection via renal secretion. The antibacterial mechanism is suggested to involve bactericidal capacities of LF, fragments thereof, or its peptides.

Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model

“…LF has a number of biological functions, including antimicrobial and immunomodulatory effects in vitro and in vivo (Brock, 1995;Tomita et al, 2002;Vorland, 1999). It has been reported that orally administered bovine LF reduces the number of pathogenic organisms not only in the gastrointestinal tract (Teraguchi et al, 1995;Wada et al, 1999) but also in tissues distant from the gastrointestinal tract in several animal models of infection (Abe et al, 2000;Bhimani et al, 1999;Haversen et al, 2000) and in humans with chronic hepatitis C and tinea pedis (Ishii et al, 2003;Iwasa et al, 2002;Yamauchi et al, 2000). It is known that LF and an LF-derived antimicrobial peptide, lactoferricin B (LFcin B), inhibit in vitro growth of fungi such as Candida albicans (Kuipers et al, 1999;Wakabayashi et al, 1996Wakabayashi et al, , 1998 and Trichophyton mentagrophytes ; it has been shown that orally administered LF shows a host-protective effect against systemic C. albicans infection in mice (Abe et al, 2000) and cutaneous T. mentagrophytes infection in guinea pigs .…”

Effect of lactoferrin feeding on the host antifungal response in guinea-pigs infected or immunised with Trichophyton mentagrophytes

“…It is thought to play an important role in host defence because it exhibits a variety of biological activities, including antimicrobial activity and immunomodulatory effects, as shown by in-vitro studies [1,2]. It is increasingly appreciated that oral administration of LF or its fragment peptides improves the survival rate and enhances elimination of pathogens from the body of animals or human patients infected with bacteria, fungi, protozoa or viruses [3][4][5][6][7]. Recent studies showed that feeding bovine LF enhances the elimination of pathogens and the rate of symptomatic cure in guinea-pigs and man with dermatophytosis, a very common fungal infection on the skin [8,9].…”

Lactoferrin and Its Role in Neonatology: A Review Article

“…In mouse experiments, oral administration of bovine LF reduced the number of bacterial infections in the gastrointestinal tract [23], while promoting the growth of bacteria with low iron requirements such as Lactobacillus and Bifidobacterium, which are generally believed to be beneficial to the host [24,25]. Oral LF was also found to be effective against experimentally induced Urinary tract infection (UTI) and endotoxin-induced septic shock [26,27]. LF also has immune-modulatory role, ascribed to its immunotropic and antiinflammatory effects [28,29].…”

“…LF or LFcin act synergistically against E. coli bacteria which are isolated from patients of bovine mastitis and human urinary tract infection [30,31]. Oral LF or derived peptides are also effective against E. coli uro-sepsis [26]. There is a presumptive hypothesis for this mechanism of action that the LF remains intact in the gastrointestinal tract and is accumulated in the blood only when the mucosal damage of GI system is seen leading to its breach in its integrity.…”