Immunology Letters, 36 (1993) 215-218 Elsevier SciencePublishers B.V. IMLET 01962 Morphine effect on proliferation of normal and tumor cells of immune origin M.G. Sergeeva, Z.V. Grishina and S.D. Varfolomeyev A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia (Received 17 November 1992; revision received4 March 1993; accepted 23 March 1993) I. Summary The influence of morphine on proliferation of human tumor K562 and lymphoid cells was stud- ied and compared with that on the mitogen-in- duced proliferation of human peripheral blood mononuclear cells (PBMC). Morphine was shown to act as a suppressor of both cellular DNA synthesis (50% and more as compared to control) and the cellular population growth of mitogen-in- duced PBMC, B-lymphoma Namalva cells and EBV-transformed lymphocytes. Morphine activat- ed proliferation of myeloid K562 and T-lympho- ma Yurkat cells 1.5-fold. It is supposed that the opposite effects of morphine on proliferation of cell lines of immune origin reveal the difference in modulation of diverse immune cell types by morphine. 2. Introduction It is known that carcinogenic events associated with human and animal neoplasias are modulated by opioid peptides and alkaloids. Opioid agonists have been implicated in the regulation of tumor growth [1,2] and significantly inhibit the growth of tumor cells in culture [3]. Key words: Immune; Morphine; Mitogen-induced prolifera- tion; Tumor growth Correspondence to: M.G. Sergeeva, A.N. Belozersky Institute of Physico-ChemicalBiology,Moscow State University, Mos- cow 119899, Russia. At the same time the effects of opioid peptides and alkaloids on the immune system have been investigated by numerous laboratories. It has been shown that chronic administration of mor- phine is accompanied by immunosuppression [4]. There are specific binding sites for opioid ligands on lymphocytes [5,6], lymphoma cells [7], Epstein- Barr (EBV)-transformed human lymphocytes [8]. Therefore opioid peptides and alkaloids can di- rectly influence normal and tumor lymphoid cells. In the present study we investigated the in- fluence of morphine on proliferation of myeloid and different lymphoid cell lines compared with that on mitogen-induced proliferation of human PBMC. 3. Materials and Methods Blood was drawn from twelve healthy volun- teers in tubes with anticoagulated supplements. PBMC were obtained by Ficoll-Hypaque density gradient centrifugation. After two washings in phosphate-buffered saline, cells were resuspended at 1 x 106 cells/ml in RPMI-1640 (Gibco) supple- mented with 10% heat-inactivated fetal calf ser- um (Serva), 2 mM L-glutamine (Gibco), 15 mM HEPES (Gibco) and antibiotics. A trypan blue test resulted in an average viability of over 95% of PBMC before culturing. Cell lines Namalva, Yurkat, K562 were ob- tained from the Institute of Immunology (Mos- cow, Russia), EBV-transformed lymphocyte lines were obtained from the National Centre of Molec- ular Diagnostics (Moscow). All cell lines were 215