We previously reported that restraint stress impairs the antitumor immune responses through its suppressive effect on the Th1-type cytokine production from CD4+ T cells. In this study, we investigated a potential of Hochu-ekki-to (TJ-41:Bu-Zhong-Yi-Qi-Tang) to restore stress-induced immunosuppression. The oral administration of TJ-41 was able to improve a decreased cellularity in the lymph node and spleen and to improve an inhibition of tumor-specific Th1-type cytokine production, both of which were induced by repeated restraint stress in tumor-bearing mice. The oral administration of TJ-41 also induced a partial recovery of the antitumor cytolytic activity in the stress-burdened tumor-bearing mice. More importantly, the growth of tumors in stress-burdened preimmunized mice was obviously inhibited by TJ-41, and resulted in tumor-free state in 75% of the mice. Regarding the mechanisms by which TJ-41 restored the antitumor responses in stress-burdened mice, we found that the serum levels of corticosterone and interleukin-12 were normalized by TJ-41. In addition, the expression of CD80 and CD86, which both decreased in the stress-burdened mice, was restored to the normal level by TJ-41. Taken together, our results indicate that the oral administration of TJ-41 is able to restore the antitumor T cell responses in stress-burdened tumor-bearing mice by normalizing the serum corticosterone, interleukin-12 and the expression of costimulatory molecules. Copyright (C) 1999 Elsevier Science B.V.
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