Antipyretic activity of gingyo-san, a traditional medicine, in influenza virus-infected mice.

Gingyo-san is composed of 10 crude drugs and used as a traditional antipyretic medicine for the treatment of the common cold and influenza virus infection. In a murine intranasal influenza infection model, fever produced by the infection has been demonstrated to be reduced by suppressing interferon-induced interleukin (IL)-1 alpha production. Thus, we focused on the serum level of IL-1 alpha which produces such novel antipyretic activity, and evaluated the relationship between defervescence and the suppression of IL-1 alpha production by Gingyo-san in influenza virus-infected mice. Fever was produced in the infected mice 33-44 h after infection. Oral administration of a hot water-extract of Gingyo-san (8.9-12.5 mg/0.25 ml/mouse x 3 per day) significantly reduced fever production and suppressed the rise in IL-1 alpha production to the level in uninfected mice. No apparent toxicity by Gingyo-san was observed in infected mice. When the hot water-extract of each 10 of the crude components of Gingyo-san (an unknown amount extracted from 6.25 mg/0.25 ml/mouse x 3 per day for Saigae Tataricae Cornu and 3.5 mg/0.25 ml/mouse x 3 per day for the other 9) was orally administered to infected mice, 6 showed significant antipyretic activity. Of these 6, Saigae Tatricae Cornu significantly suppressed the rise in IL-1 alpha production to the basal level while the other 5 did not affect serum IL-1 alpha. Thus, of the 10 crude components of Gingyo-san, Saigae Tataricae Cornu simultaneously exhibited antipyretic and IL-1 alpha-regulatory activities. The novel antipyretic action of Gingyo-san may be mainly mediated by Saigae Tataricae Cornu which regulates the elevated serum IL-1 alpha level produced by influenza infection.