Z-100, a polysaccharide-rich preparation extracted from the human typeMycobacterium tuberculosis, improves the resistance of Meth-A tumor-bearing mice to endogenous septic infection |
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Authors: | Hidetaka Sasaki Makiko Kobayashi Yutaka Emori Osamu Ohya Yoshiro Hayashi Ph D Kikuo Nomoto |
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Institution: | (1) Immunological section, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1 Oshikiri, Kohnan-machi Ohsato-gun, 360-01 Saitama, Japan;(2) Department of Immunology, Institute of Bioregulation, Kyushu University, Maida-shi 3-1-1, Higashi-ku, 812 Fukuoka, Japan |
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Abstract: | The effect of Z-100, an immunomodulatory arabinomannan extracted fromMycobacterium 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 × 107 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. |
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Keywords: | Z-100 Immunomodulator Suppressor cell Opportunistic infection Mycobacterium tuberculosis |
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