Effect of Z-100, an immunomodulator extracted from human type tubercle bacilli, on the pulmonary metastases of Lewis lung carcinoma in attempt to regulate suppressor T cells and suppressor factor, IL-4.
In the present study, anti-metastatic effect of Z-100 on the spontaneous pulmonary metastases of Lewis lung carcinoma (3LL) was examined in an attempt to regulate suppressor T cells. When Z-100 (10 mg/kg) was daily injected i.p. after 3LL inoculation, survival rate of these mice was increased significantly (p < 0.05). In addition, the number of pulmonary metastatic colonies of 3LL in Z-100-treated mice were significantly decreased by 38% at 21 days, as compared with that of control mice (p < 0.05). Along with the decrease of pulmonary metastases, suppressor cell activity was also gradually reduced in these mice, as compared with that of control mice. When splenic suppressor cells (5 x 10(7) cells) from 3LL-bearing mice were adoptively transferred into normal mice (recipients) just before inoculation of 3LL, the development of pulmonary metastases in recipients was significantly accelerated. However, splenocytes from 3LL-bearing mice treated with Z-100 did not affect the development of pulmonary metastasis. The potential to accelerate the metastasis of splenic mononuclear cells from 3LL-bearing mice was decreased significantly by the treatment with anti-Thy 1.2 monoclonal antibody (mAb), anti-Lyt 2.2 mAb or anti-CD 11b mAb followed by complement. IL-4 activity in the sera of 3LL-bearing mice was detected 15 days after tumor inoculation (13 pg/ml) and gradually increased (18 pg/ml) 20 days after tumor inoculation. However, when Z-100 (10 mg/kg) was daily injected i.p., IL-4 activity in sera was decreased significantly, and the IL-4 activity was not detected in these mice on day 20. These results suggest that Z-100 could inhibit the pulmonary metastases in 3LL-bearing mice through the inhibition of suppressor T cell activity and a possible candidate of its effector molecule, IL-4.
Emori
Y
Y
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Sasaki
H
H
Hayashi
Y
Y
Nomoto
K
K
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D019264:Adoptive Transfer; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000097:blood; D008055:Lipids / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D008351:Mannans / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D008055:Lipids; D008351:Mannans; C031208:specific substance maruyama; D015847:Interleukin-4