Abstract
Background. A Kampo medicine, Shahakusan (SHS), has been prescribed in late phase of infection that causes inflammations in the lung. But effect of SHS on viral infection in respiratory tract has never been reported. Objectives. To evaluate anti-influenza virus activity of SHS and its mode of actions through immune systems. Methods. SHS (0.3 g/kg/day) was orally administered to BALB/c miceforupper (URI) or lower respiratory tract infection (LRI) of influenza virus A/PR/8/34. The virus titer of nasal lavage fluid (NLF) at 5 or 2 day postinfection (p.i.) and cytokine mRNA expressions in mandibular lymph node or lung at 5 or 4 day p.i. were evaluated for URI or LRI, respectively. The histopathological examinations of lung tissue and NK cell activity in the splenocytes were also evaluated at 4 day p.i. on LRI. Results. When SHS was administered from 7 days before to 4 days p.i. for URI, the virus titer was significantly decreased in comparison with water-treated control, and IL-4, IL-1β, and IL-10 mRNA expression was decreased, but IL-12A mRNA expression was increased. Administration of SHS from one day before to one day p.i. for LRI significantly decreased the virus titer. SHS also decreased infiltration of inflammatory cells in the bronchoalveolar spaces and damage of desquamated mucosal epithelia of bronchiole, decreased IP-10 mRNA expression, and increased NK cell activity. Conclusion. SHS has no direct effect on influenza virus infection but exerts antiviral effect in mice by its immunomodulating activity through action of NK cells and anti-inflammatory activity in the lung.
Highlights
Influenza is a viral infection that affects mainly upper respiratory tract
It has been reported that around 80% of mortality by influenza virus infection is caused by pneumonia [2, 3]
Antipyretic potency of Maoto (Mahuang-tang in Chinese) in human [8, 22] and Gingyosan (Yin-qiao-san in Chinese) in mice [23, 24] have been reported, Kakkonto (Ge-gen-tang in Chinese) has increased IL-12 production in the bronchoalveolar lavage fluid (BALF) of mice [25], and Shoseiryuto (Xiao-qing-long-tang in Chinese) has augmented anti-influenza virus IgA antibody followed by alleviation of the proliferation of influenza virus in the respiratory tract of mice [26,27,28]
Summary
Influenza is a viral infection that affects mainly upper respiratory tract. Influenza infection usually lasts for about one to two weeks and is characterized by sudden onset of high fever, followed by myalgia, headache, and severe malaise, nonproductive cough, sore throat, and rhinitis [1]. Effect of SHS on viral infection in respiratory tract has never been reported. To evaluate anti-influenza virus activity of SHS and its mode of actions through immune systems. SHS (0.3 g/kg/day) was orally administered to BALB/c micefor upper (URI) or lower respiratory tract infection (LRI) of influenza virus A/PR/8/34. The virus titer of nasal lavage fluid (NLF) at 5 or 2 day postinfection (p.i.) and cytokine mRNA expressions in mandibular lymph node or lung at 5 or 4 day p.i. were evaluated for URI or LRI, respectively. SHS has no direct effect on influenza virus infection but exerts antiviral effect in mice by its immunomodulating activity through action of NK cells and anti-inflammatory activity in the lung
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