Influence of various cytokines on the induction of lymphokine-activated killer cells.

The clinical use of interleukin-2 (IL-2) for generation and activation of cytotoxic lymphocytes lymphokine-activated killer cells (LAK) has principally demonstrated that tumors can be restricted by modulation of the immune system. However, innovative approaches are required to improve the therapeutic results. In this connection, combinations of IL-2 with other cytokines may be of interest to increase the numbers and cytotoxic activity of LAK. On the other hand, IL-2 itself mediates immune reactions and secretion of various cytokines. Therefore, we investigated the effect of interferon-alpha (IFN-alpha), IFN-gamma and tumor necrosis factor (TNF-alpha) on the induction of LAK activity by IL-2, and the induction of IFN-gamma and TNF-alpha by IL-2. LAK activity could not be enhanced by IFN-gamma and TNF-alpha, but was enhanced by IFN-alpha. This may in part be due to the fact that IL-2 itself induces high amounts of TNF-alpha and IFN-gamma. Besides the effect of IFN-alpha on LAK activity, an increased susceptibility of tumor cells for LAK in vitro could be achieved by preincubation of tumor cells with IFN-alpha. This mechanism seems not to be related to an increased expression of MHC class I and II antigens.