In vitro stimulation of human granulocytes and lymphocytes by pico- and femtogram quantities of cytostatic agents.

The influence of a broad concentration range of naturally occurring naphthoquinones and other cytotoxic or cytostatic agents (azathioprine, colchicine, cyclophosphamide, fluorouracil, methotrexate and vincristine) on human granulocytes and lymphocytes was investigated in a systematic in vitro study. At high concentrations (100 micrograms-10 ng/ml) nearly all substances showed the known cytotoxic or immunosuppressive effects, whereas most of the same compounds displayed immunostimulating activities at very low concentrations (10 ng-10 fg/ml). After a cold shock or heat treatment lymphocytes became more sensitive against these compounds in the active concentration range than untreated cells. These results possibly give an explanation for the antitumour activity of some plant extracts, for which a direct cytotoxicity due to the applied low dose can be excluded.