The augmentation of resistance against Listeria monocytogenes after an intraperitoneal (ip) administration of
shosaiko-to in mice was shown to depend on the time interval between the treatment and the
infection. A maximal effect was expressed in mice treated 4 days before ip
infection. The time dependent resistance correlated to the accumulation of macrophages in the peritoneal cavity just before the
infection, but not to bactericidal activity as judged by the fact that peritoneal macrophages from untreated mice and those from mice treated with
shosaiko-to 4 days before showed a high bactericidal activity of the same degree. Resistance to the
infection in untreated mice may be attributable to newly accumulating macrophages with a low level of bactericidal activity, but not to resident macrophages with a high level of the activity. After intravenous
infection, on the other hand, a maximal effect was expressed in mice treated with
shosaiko-to 2 days before. The resistance correlated to accumulation of macrophages and bactericidal activity in the spleen just before the
infection. Participation of
cytokines in an augmenting effect of
shosaiko-to on protection against the
infection was examined.
Shosaiko-to induced a transient elevation of serum CSF activity that was maximal at 3 hours after the administration in uninfected mice, though it did not augment the CSF activity induced by the
infection. The elevation of CSF activity may induce accumulation of macrophages with a high level of bactericidal activity in the spleen 2 days after administration of
shosaiko-to and then in the peritoneal cavity 4 days after administration. IFN-gamma and
TNF-alpha did not participate in the effect because administration of anti-IFN-gamma or anti-
TNF-alpha just before administration of
shosaiko-to or just before
infection did not abrogate the inhibitory effect of
shosaiko-to on the bacterial growth in the early stage of
infection.
Shosaiko-to also induced an increase of CFUm number in the spleen. The effect may contribute to the augmentation of resistance in the late stage of
infection by differentiating to mature macrophages.