Z-100, a polysaccharide-rich preparation extracted from the human type Mycobacterium tuberculosis, improves the resistance of Meth-A tumor-bearing mice to endogenous septic infection.
The effect of Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis, on cecal ligation and puncture (CLP)-induced sepsis in mice bearing Meth-A fibrosarcoma was investigated. When normal BALB/c mice were subjected to the CLP procedure, their mortality rate was 17%. On the other hand, an increased mortality was observed in tumor-bearing mice subjected to CLP 10 days after tumor inoculation, and then all mice died when tumor-bearing mice were subjected to CLP 20 days after tumor inoculation. However, the increased percent mortality was decreased by 50% when these mice were injected intraperitoneally with a 10 mg/kg dose of Z-100. When splenocytes (5 x 10(7) cells), obtained from Meth-A tumor-bearing mice 20 days after tumor inoculation, were transferred intravenously to normal mice (recipient mice), mortality of these recipient mice were increased by 62% as compared with that of the control (22%). However, no increased mortality (25%) was observed in recipient mice which were transferred with splenocytes from tumor-bearing mice injected intraperitoneally with Z-100 (10 mg/kg). In addition, suppressor cell activity was demonstrated in splenocytes from Meth-A tumor-bearing mice at 20 days after tumor inoculation using one-way mixed lymphocyte reaction. However, the suppressor cell activity was significantly decreased by the intraperitoneal administration of a 10 mg/kg dose of Z-100 (p < 0.01). The increase of mortality in recipient mice by adoptive transfer of mononuclear cells (MNCs) from tumor-bearing mice was not detected when these MNCs were treated with anti-Thy 1.2 monoclonal antibody (mAb), anti-Lyt 2.2 mAb or anti-CD11b mAb, but an increase was seen with anti-Lyt 1.2 mAb or anti-immunoglobulin antiserum treated MNCs. These results suggest that the suppressor cells affect the mortality of CLP-induced sepsis and Z-100 may have a therapeutic activity against opportunistic infections in immunocompromised hosts through the regulation of suppressor T-cells.
Sasaki
H
H
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Kobayashi
M
M
Emori
Y
Y
Ohya
O
O
Hayashi
Y
Y
Nomoto
K
K
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D002432:Cecum; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D008026:Ligation; D008055:Lipids / Q000627:therapeutic use*; D008297:Male; D008351:Mannans / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D011677:Punctures; D018805:Sepsis / Q000209:etiology / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D008055:Lipids; D008351:Mannans; C031208:specific substance maruyama