Restoring Natural Killer Cell Cytotoxicity After Hyperthermia Alone or Combined with Radiotherapy

Background: The aim of the present study was to investigate in vitro the effect of hypo-and hyperthermia alone or in combination with irradiation on natural killer cell (NK) cytotoxicity, recovery of this function and the possibility of preventing damage to or enhancing cytotoxicity recovery using interferons (IFNs) alpha, beta, and gamma and interleukin-2 (IL-2). Materials and Methods: We used non-selected NK cells and measured their cytotoxicity using the Cr-51 release assay. Temperatures ranging from 31-45 degrees C and thermal treatment times from 0-180 min were assessed. IFNs were applied at concentrations from 0-1,000 IU/ml and IL-2 from 0-450 IU/ml. The range of irradiation dose was from 0-30 Gy. Results: We detected no significant differences in cytotoxicity at temperatures from 31-37 degrees C. The most significant decrease in cytotoxicity was observed between 41 and 42 degrees C (p=0.0010), and heating NK cells at 42 degrees C for 180 min almost completely abolished this function. NK cell cytotoxicity largely recovered during the first 24 h, depending on the heating time. IFN-alpha, beta, and gamma demonstrated no concentration-dependent ability to aid in recovery when used before or after the thermal treatment. In contrast, IL-2 restored cytotoxicity in a concentrationand incubation time-dependent manner and was equally active when used before, during or after heating. NK cells were heated at 42 degrees C for various times and then irradiated with a single dose or first irradiated and then heated; however, no statistically significant differences were observed (p=0.520). An approach of IL-2 treatment followed by radiation and heating was the most effective in restoring NK cytotoxicity (p=0.000). Conclusion: NK cell cytotoxicity is impaired in vitro at 42 degrees C and above, with possible partial recovery. IL-2, but not IFNs, was able to restore NK cell cytotoxicity in a concentration-dependent manner. IL-2 can also reverse the damage caused by combined hyperthermia and irradiation.