Purified podophyllotoxin (CPH-86) inhibits lymphocyte proliferation but augments macrophage proliferation |
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| Authors: | Q Y Zheng M Wiranowska J R Sadlik J W Hadden |
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| Affiliation: | 1. Department of Chemistry, Kakatiya University, Warangal 506009, India;2. Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India;3. School of Pharmaceutical Education and Research (SPER), Jamia Hamdard, New Delhi 110062, India;1. Gansu Provincial Key Lab of Arid Land Crop Science/College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, PR China;2. Texas Tech University, Department of Chemistry and Biochemistry, TX 79409, USA;3. Station of Industrial Crop Promotion of Gansu province, Lanzhou 730000, PR China;4. College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730000, PR China;1. Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA;2. National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, 38677, USA;3. Institute for Drug Delivery & Biomedical Research, Bangalore, India;1. Department of Chemistry, Innovative Drug Research Center, College of Sciences, Shanghai University, Shanghai 200444, China;2. Nano Science and Technology Institute, University of Science and Technology of China, Suzhou 215123, China;3. Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025, China;4. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China |
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| Abstract: | Purified podophyllotoxin (CPH-86) is an inhibitor of microtubular aggregation used in the treatment of cancer, psoriasis and rheumatoid arthritis. To better understand its immunopharmacology we examined its effects on human lymphocytes and monocytes and guinea pig macrophages. CPH-86 inhibits mitogen-induced human lymphocyte proliferation and macrophage growth factor-stimulated macrophage proliferation with ID50s of approximately 10(-7) M. The effect of CPH-86 on lymphocytes in conjunction with mitogen is nonlethal, evident during the early but not the late phases of proliferation, and associated with early increases in cyclic AMP levels. In contrast to these obviously inhibitory effects, CPH-86 (10(-7) M) alone induces IL-1 by human monocytes and, with mitogen, it induces IL-2 production by human lymphocytes. It directly stimulates macrophage proliferation and potentiates the effects of low doses of macrophage growth factor to do so. The latter effects may be mediated by colony stimulating factor production. The effects of CPH-86 are not mediated by inhibition of prostaglandin synthesis. The stimulation of monokine and lymphokine production by CPH-86 may represent positive features of its action and may be immunotherapeutic. |
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