EFFECT OF TNF-ALPHA AND IFN-ALPHA ON THE PROLIFERATION AND CYTOTOXICITY OF LYMPHOKINE-ACTIVATED KILLER IN PATIENTS WITH BLADDER-CANCER

Objective To investigate the effects of interleukin-2 (IL-2) combined with either tumor necrosis factor-alpha (TNF-alpha) or alpha-interfero n (IFN-alpha) on the proliferation and cytolysis to bladder tumor cell s of lymphokine-activated killer (LAK) cells in patients with bladder cancer. Methods LAK cells were generated by ficoll-paque density-centr ifugation from 21 patients with bladder cancer and cultured in medium containing IL-2. LAK cell proliferation was assayed in the presence of various concentrations of either TNF-alpha or IFN-alpha by cell count in 96-well plates. Bladder cancer cell lines BIU-87 and EJ were cultu red as target cells and the cytotoxicity of LAK cells was determined b y 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) a ssay. Results The proliferation of LAK cells induced by IL-2 was enhan ced by TNF-alpha in a dose-responsive fashion. The direct growth suppo rt for the LAK cells was also observed with IFN-alpha at the concentra tion of 1000 U/ml after 48 hours oi culture. TNF-alpha (5000 U/ml) res ulted in an increase in the cytotoxicity of LAK cells to BIU-87 and EJ cells. However, the change of cytotoxicity of LAK cells treated with IFN-alpha was not statistically significant. Conclusions TNF-alpha and IFN-alpha enhance the proliferation and activation of LAK cells and i nfluence their antitumor cytotoxicity in patients with bladder cancer.