In vitro effect of hyperthermia on natural cell-mediated cytotoxicity

It is well known that hyperthermia (HY), which is used for the treatment of cancer; depresses natural cell-mediated immunity in vitro. Experiments wer e performed to confirm the inhibitory effect of HY (42 degrees C for I hour ;) on natural killer (NK) activity and to evaluate the influence of HY on t he generation and cytotoxic activity of interleukin-2 (IL-2)-activated NK c ells. Additional experiments were also carried out to evaluate the effect o f a simultaneous exposure of effector and target cells to MY: The results s howed that HY profoundly reduced the lytic activity of NK cells and demonst rated that this inhibition was transient and not due to an apoptosis-induce d reduction of the number of effector cells. Moreover; the exposure of mono nuclear mononuclear cells to KY before IL-2 stimulation did not affect the generation of IL-2-activated NK cells, whereas, the hyperthermic treatment of IL-2-activated NK cells produced a mal ked reduction of their cytotoxic activity. The results also showed that the simultaneous exposure of effecto r and target cells to HI: during the cytotoxicity assay, produced a marked reduction of lytic activity of NK and IL-2-activated NK cells, and that thi s impairment was specific for effector. cells. In this context, heat-exposu re of target cells alone, did not substantially modify their susceptibility to lysis induced by either NK ol IL-2-activated NK cells. These results ad d further evidence of MY-induced inhibition of natural cell-mediated immuni ty, and suggest that, in the course of therapeutic HY, immune response coul d be significantly altered.