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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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 Imakita, Yoshiko Fukuda, Yukio Watanabe and Kimiyasu Shiraki
Journal of Pharmacology and Experimental Therapeutics July 2001, 298 (1) 362-368;
Minako Tsurita
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Masahiko Kurokawa
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Masami Imakita
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Yoshiko Fukuda
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Yukio Watanabe
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Kimiyasu Shiraki
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Abstract

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-γ 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.

Footnotes

  • ↵1 Current address: Rinku General Medical Center, Ouraikita 2-23, Izumisano, Osaka, Japan.

  • Abbreviations:
    IFN
    interferon
    ANOVA
    analysis of variance
    BALF
    bronchoalveolar lavage fluid
    CAM
    clarithromycin
    CC50
    the concentration of CAM reducing cell viability by 50%
    CTL
    cytotoxic T lymphocyte
    IL
    interleukin
    MDCK
    Madin-Darby canine kidney
    PBS
    phosphate-buffered saline
    PFU
    plaque-forming units
    NO
    nitric oxide
    ELISA
    enzyme-linked immunosorbent assay
    • Received December 12, 2000.
    • Accepted March 11, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 1
1 Jul 2001
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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 Imakita, Yoshiko Fukuda, Yukio Watanabe and Kimiyasu Shiraki
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 362-368;

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

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 Imakita, Yoshiko Fukuda, Yukio Watanabe and Kimiyasu Shiraki
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 362-368;
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