Modulation of lung local immune responses by oral administration of a herbal medicine Sho-saiko-to.

Sho-saiko-to (SST), a Chinese/Japanese herbal medicine (Kampo medicine) widely used to treat chronic hepatitis in Japan, is known to modulate immune responses, and thus its immunomodulating activity may be responsible for its bi-directional effects on the lungs as therapeutic efficacy in various lung diseases and involvement in development of interstitial pneumonia. We administered SST to BALB/c mice orally and examined the lung tissue levels of pro/anti-inflammatory cytokines, interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and the effects of SST on acute lung injury induced by instillation of lipopolysaccharide (LPS) or IL-1. Although SST had no effect on lung TNF-alpha or IL-1beta level, it increased IL-6. Investigation of active fractions of SST suggested that multiple ingredients were supposed to be responsible for IL-6-inducing activity. Liquiritigenin, a metabolite of liquiritin which is one of the major ingredients in SST enhanced in vitro IL-6 production in anti-CD3 monoclonal antibody (anti-CD3 mAb)-stimulated lung mononuclear cells in a cell-type specific and dose-dependent manner. SST suppressed LPS-induced lung injury at the later phase when lung leak was evident while being ineffective on initial neutrophil sequestration to the lung in these models. These findings suggest that SST modulates lung inflammation by regulating local immune response.