Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice

1 Nutritional Science Laboratory, Morinaga Milk Industry Co. Ltd, 5-1-83 Higashihara, Zama, Kanagawa 228-8583, Japan 2 Department of Virology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan Correspondence Kouichirou Shin k_shin{at}morinagamilk.co.jp Received January 19, 2005 Accepted April 18, 2005 Milk contains a wide variety of host protective factors against infectious microbes. Among these protective factors, lactoferrin (LF) and lactoperoxidase (LPO) have been reported to exhibit antiviral activities as well as immuno-modulatory effects. In the present study, the effects of orally administered LF and LPO were assessed in a mouse influenza virus infection model. BALB/c mice were intranasally infected with 6.6 x 10 2 p.f.u. of influenza virus A/PR/8/34(H1N1). Bovine LF or LPO was administered once daily at a dose of 62.5 mg per mouse by gavage, starting 1 day before infection. Mice given LF or LPO showed a significantly lower lung consolidation score on day 6 after infection compared with the control mice that were given water instead. Concurrently, the number of infiltrated leukocytes recovered from bronchoalveolar lavage fluid (BALF) on day 6 was significantly lower in mice given LF or LPO. However, the virus yield in the BALF was not affected by these treatments. The serum level of IL-6, a pro-inflammatory cytokine, positively correlated with the lung consolidation score in each group and was significantly lower on day 6 in the mice given LPO. These results suggest the potential of oral administration of LF or LPO to attenuate pneumonia in influenza-virus-infected mice through the suppression of infiltration of inflammatory cells in the lung. Present address: Department of Pharmacology, Kyushu University of Health and Welfare, 1714-1 Yoshino-Machi, Nobeoka, Miyazaki 882-8508, Japan. Abbreviations: BALF, bronchoalveolar lavage fluid; IL, interleukin; LF, lactoferrin; LPO, lactoperoxidase; TNF, tumour necrosis factor.