Objective: To investigate the effects of interleukin-2 (IL-2) combined with either tumor necrosis factor-alpha (TNF-alpha) or alpha-interferon (IFN-alpha) on the proliferation and cytolysis to bladder tumor cells of lymphokine-activated killer (LAK) cells in patients with bladder cancer.
Methods: LAK cells were generated by ficoll-paque density-centrifugation 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 cultured as target cells and the cytotoxicity of LAK cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay.
Results: The proliferation of LAK cells induced by IL-2 was enhanced by TNF-alpha in a dose-responsive fashion. The direct growth support for the LAK cells was also observed with IFN-alpha at the concentration of 1000 U/ml after 48 hours of culture. TNF-alpha (5000 U/ml) resulted 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 influence their antitumor cytotoxicity in patients with bladder cancer.