Immunomodulating Effects of Bleomycin and its Derivatives, Peplomycin and Liblomycin on Murine Antitumour Effector Cells

Xiao-Mei Chen, Qing Wang, Rui-Kun He, Yu-Tao Li, Xiao-Yun Chen, Hiroshi Kurihara, Rong-Rong He, Yi-Fang Li
unpublished
INTRODUCTION Bleomycin (BLM) is an antitumour agent, which is well known for its various immunoaugmenting effects 1 such as the enhancement of interleukin-2 (IL-2) production by mitogen-stimulated spleen cells 2 , activation of macrophages 3 and the elimination of suppressor T-lymphocyte activity which might aid the host in overcoming immunosuppression 4. Its clinical use, however, is limited by toxicity to the lungs in the form of lung fibrosis 5. Peplomycin (PEP), an analogue of BLM, has a
more » ... er pulmonary toxicity than BLM, but this toxicity remains a major dose-limiting factor of this drug. Liblomycin (LIB) is a novel analogue of BLM and exhibits a broader antitumour spectrum as well as an extremely weaker pulmonary toxicity than BLM and PEP 6 (Fig. 1). Furthermore, it has been widely reported that LIB is generally more effective against some BLM or PEP-unresponsive tumour lines, both in vitro and in vivo. LIB also exhibits such properties as a greater cellular drug uptake and resistance to BLM hydrolase 7. The previous study has reported that BLM and PEP increase IL-2, tumour necrosis factor (TNF) and interferon (IFN) release during mitogen-stimulated rat spleen cell culture, whereas, cytokine release decreased after treatment with LIB 8. Therefore, in this study, we compared equivalent doses of LIB, PEP and BLM for their effects on mouse natural killer (NK) and lymphokine-activated killer (LAK) precursor cell activities and also for cytokine production in vivo. The results indicate that while BLM has an immunoenhancing effect in the mouse, PEP has a negligible effect while LIB causes immunosup-pression. These immunosuppressive effects of LIB may be attributed to the efficacy of the antitumour agent as a drug.
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