Vol. 298, Issue 1, 362-368, July 2001

Early Augmentation of Interleukin (IL)-12 Level in the Airway of Mice Administered Orally with Clarithromycin or Intranasally with IL-12 Results in Alleviation of Influenza Infection

Minako Tsurita , Masahiko Kurokawa, Masami Imakita¹ , Yoshiko Fukuda, Yukio Watanabe and Kimiyasu Shiraki

Departments of Virology (M.T., M.K., Y.F., K.S.) and Otorhinolaryngology (M.T., Y.W.), Toyama Medical and Pharmaceutical University, Toyama, Japan; and Division of Pathology (M.I.), National Cardiovascular Center, Osaka, Japan

The protective role of interleukin (IL)-12 against influenza infection was assessed by analyzing the efficacies of orally administered clarithromycin (CAM) as an immunomodulator and intranasal administration of recombinant IL-12 in intranasally influenza virus-infected mice. In infected mice, CAM at 20 mg/mouse/day significantly elevated the levels of IL-12 and interferon- on days 2 and 3, respectively, after infection in the bronchoalveolar lavage fluid (BALF), but the levels in the sera were not affected. The levels of IL-4, -6, and -10 were not significantly affected in the sera and BALF. Corresponding with the local elevation of IL-12 level, CAM reduced virus yield and the number of infiltrated cells in the BALF, the severity of pneumonia, and mortality of the treated mice. The potential activity of CAM as an experimental immunomodulator was verified at a dose of 20 mg/mouse/day. Intranasal administration of the optimal dose (20 ng/mouse) of IL-12 on day 2 significantly reduced virus yield in the BALF after infection. The loss of body weight was significantly suppressed by IL-12 administration. The local elevation of IL-12 level at the optimal dose and timing in influenza infection was confirmed to be effective in alleviating the influenza infection in mice treated with the two different ways. Thus, the augmentation of IL-12 production or administration of supplementary IL-12 in the respiratory tract was essential in reducing virus yield in the early phase of influenza and may be crucial for recovery from influenza infection.