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.

Abstract

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.

• Authors: Y Emori, H Sasaki, Y Hayashi, K Nomoto
• Journal: Biotherapy (Dordrecht, Netherlands) (Biotherapy) Vol. 9 Issue 4 Pg. 249-56 ( 1996) ISSN: 0921-299X [Print] Netherlands
• PMID: 9012544 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antineoplastic Agents
• Lipids
• Mannans
• specific substance maruyama
• Interleukin-4

Topics

• Adjuvants, Immunologic (therapeutic use)
• Adoptive Transfer
• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Lewis Lung (drug therapy)
• Humans
• Interleukin-4 (antagonists & inhibitors, blood)
• Lipids (pharmacology, therapeutic use)
• Lung Neoplasms (secondary)
• Male
• Mannans (pharmacology, therapeutic use)
• Mice
• Mice, Inbred C57BL
• T-Lymphocytes, Regulatory (drug effects, immunology)