On the other hand, another investigation reported that human lactoferrin promotes the binding of adenovirus to human corneal epithelial cells and also infection of the cells by adenovirus [38]. In this experimental system, there was no data on bovine lactoferrin. The anti-enteroviral activities of lactoferrin are indicated in poliovirus, enterovirus 71, coxsackievirus A16, echovirus 5, and echovirus selleck chemical 6 [39], [40], [41], [42], [43] and [44]. Remarkably, bovine lactoferrin induced IFN-α expression of human neuroblastoma cells (SK-N-SH) and inhibited enterovirus
71-induced interleukin (IL)-6 production [41]. The antiviral activity of bovine lactoferrin was not obvious in echovirus 9 [40]. Following enterovirus 71 infection, neonatal pups ingesting transgenic milk expressed recombinant porcine lactoferrin showed significantly higher survival rate and heavier body weight compared to wild-type mice [45] (Table 2). On the other hand, oral supplementation of bovine
lactoferrin at a dose of 70 mg/day did not show beneficial effects in the prevention of enterovirus 71 or rotavirus infection in children [46]. Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) establish life-long latent infections in the host and can re-emerge periodically throughout life, primarily causing facial and genital herpetic lesions, respectively. The I-BET-762 in vitro anti-herpes activities of lactoferrin have been studied in HSV-1 [47], [48], [49], [50], [51], [52], [53] and [54] and HSV-2 [49], [53] and [55] (Table 1). The effect of orally administered lactoferrin in HSV infection has been reported in one study [56] (Table 2). This study indicated that lactoferrin administration prevents Ribonuclease T1 body weight loss and increases the production of Th1 cytokines, including
IFN-γ, IL-12, and IL-18, after HSV-1 cutaneous infection in mice. These enhanced Th1 cytokine responses may help host protection against HSV-1 infection. Lactoferrin exhibits inhibitory activities against a wide range of viruses in vitro. The effects of lactoferrin oral administration have been studied in various viral infections in animals and humans. These infections included life-threating chronic hepatitis C [57], but no significant efficacy of lactoferrin was demonstrated in a clinical study with a relatively large number of patients [58]. On the other hand, the beneficial effects of lactoferrin have recently been found in common viral infections including the common cold, influenza, viral gastroenteritis, summer cold, and herpes. As lactoferrin is a food component, it is easily consumed by an individual to prevent these infections. Although the mechanism of action of lactoferrin has not been fully elucidated, direct antiviral activities exerted in the gastro-intestinal tract and systemic immune-modulation seem to be involved in these effects.