EFFECTS OF COLONY-STIMULATING FACTORS ON CELLULAR CYTOTOXICITY

Colony-stimulating factors (CSF) are used clinically in the treatment of chemotherapy-induced myelosuppression and in support of bone marrow transplantation. As CSF are known to have pleiotropic functions, thei r effects on cellular cytotoxicity were analysed in vitro against blad der carcinoma cell lines. By means of an L-[H-3]methionine-release ass ay, the cytotoxicity of peripheral blood mononuclear cells against the natural-killer(NK)-cell-resistant bladder carcinoma cell lines BT-A a nd SBC-7 was measured using different effector/target-cell ratios. Cos timulatory effects of granulocyte-colony-stimulating factor (G-CSF), g ranulocyte/macrophage-colony-stimulating factor (GM-CSF), interleukin- 3 (IL-3) and stem cell factor (SCF) on the generation of lymphokine-ac tivated killer (LAK), bacillus Calmette-Guerin-activated killer (BAK) and natural killer (NK) cell cytotoxicity were investigated in this as say. Furthermore, the effect of CSF on proliferation of urothelial tum or cells in vitro was determined by a [H-3]thymidine DNA-labelling tec hnique. GM-CSF but not G-CSF, IL-3 or SCF, was able to increase NK, BA K and LAK cytotoxicity in a dose-dependent manner. No acceleration of carcinoma cell proliferation was evident under the conditions of our a ssay. These data indicate the costimulatory effect of GM-CSF on cellul ar cytotoxicity, which might be used for immunotherapeutic purposes.