An immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis, Z-100, restores the balance of Th1/Th2 cell responses in tumor bearing mice.
The regulatory effect of Z-100 on the balance of Th1/Th2 cell responses in BALB/c mice bearing Meth-A fibrosarcoma was investigated. In tumor bearing mice, Th1 cytokine production (IL-2, IFN-gamma) are suppressed and Th2 cytokine production (IL-4, IL-10) are increased, as compared with those of normal mice. The administration of Z-100 (10 mg/kg) to tumor bearing mice restored the balance of Th1/Th2 cell responses from Th2 dominant state to the normal state. This regulatory effect of Z-100 was eliminated by depletion of adherent cells from splenocytes derived from tumor bearing mice, and by the treatment with 2-ClAdo (a macrophage inhibitor). Similarly, this regulatory effect was diminished by the treatment with anti-IL-12 mAb and anti-IFN-gamma mAb. In addition, the IL-12 p40 mRNA expression in splenic adherent cells and IFN-gamma mRNA expression in CD4+ T cells were increased by the administration of Z-100 to tumor bearing mice. These results suggested that Z-100 restored the balance of Th1/Th2 cell responses to the normal one in tumor bearing mice through the activation of macrophages and up-regulation of IL-12 production from macrophages and IFN-gamma production from CD4+ T cells.
Oka
H
H
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Ohsato-gun, Saitama, Japan.
Emori
Y
Y
Ohya
O
O
Kobayashi
N
N
Sasaki
H
H
Tanaka
Y
Y
Hayashi
Y
Y
Nomoto
K
K
D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005354:Fibrosarcoma / Q000276:immunology*; D008055:Lipids / Q000302:isolation & purification / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008351:Mannans / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016207:Cytokines; D017931:DNA Primers; D008055:Lipids; D008351:Mannans; D012333:RNA, Messenger; C031208:specific substance maruyama; C012189:arabinomannan