The restoration of the antitumor T cell response from stress-induced suppression using a traditional Chinese herbal medicine Hochu-ekki-to (TJ-41:Bu-Zhong-Yi-Qi-Tang).
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.
Li
T
T
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Tamada
K
K
Abe
K
K
Tada
H
H
Onoe
Y
Y
Tatsugami
K
K
Harada
M
M
Kubo
C
C
Nomoto
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D013312:Stress, Physiological / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D004365:Drugs, Chinese Herbal; D018664:Interleukin-12; D003345:Corticosterone