title: Restoring Natural Killer Cell Cytotoxicity After Hyperthermia Alone or Combined with Radiotherapy.
abstract: 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) α, β, and γ and interleukin-2 (IL-2).
  
  
  METHODS
  We used non-selected NK cells and measured their cytotoxicity using the (51)Cr release assay. Temperatures ranging from 31-45°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°C. The most significant decrease in cytotoxicity was observed between 41 and 42°C (p=0.0010), and heating NK cells at 42°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-α, β, and γ 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 concentration- and incubation time-dependent manner and was equally active when used before, during or after heating. NK cells were heated at 42°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).
  
  
  CONCLUSIONS
  NK cell cytotoxicity is impaired in vitro at 42°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.
authors: Department of Oncology, School of Medicine, University of Tampere, Tampere, Finland hietanen.tenho.e@student.uta.fi.
authors: Tenho
authors: T
authors: Hietanen
authors: Department of Oncology, Tampere University Hospital, Tampere, Finland Department of Medical Physics, Tampere University Hospital, Tampere, Finland.
authors: Mika
authors: M
authors: Kapanen
authors: Department of Oncology, School of Medicine, University of Tampere, Tampere, Finland Department of Oncology, Tampere University Hospital, Tampere, Finland.
authors: Pirkko-Liisa
authors: PL
authors: Kellokumpu-Lehtinen
mesh_terms: D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005334:Fever; D005720:Gamma Rays; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects
chemical_list: D007376:Interleukin-2; D007372:Interferons
keywords: IL-2; Natural killer cells; cytotoxicity; hyperthermia; interferon; irradiation