PMID- 29374687 OWN - NLM STAT- MEDLINE DCOM- 20180208 LR - 20180208 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 38 IP - 2 DP - 2018 Feb TI - Natural Killer Cell Viability After Hyperthermia Alone or Combined with Radiotherapy with or without Cytokines. PG - 655-663 AB - BACKGROUND: The effects of hyperthermia and irradiation, alone and in combination, on natural killer (NK) cell viability were investigated in vitro. The roles of interleukin-2 (IL-2) and interferon (IFN) alpha, beta and gamma in rescuing NK cells from hyperthermia and irradiation were studied. MATERIALS AND METHODS: Non-selected NK cells were used as effector cells and K-562 cells as target cells. NK and K-562 cells were treated at 37 to 45 degrees C for 0 to 180 min. The cells were irradiated at room temperature using single doses from 0 to 60 Gy. Recombinant IL-2 at 100 to 450 U/ml and recombinant IFNalpha, beta and gamma at 1,000 U/ml were used for different periods of time. NK cell viability was measured by intracellular adenosine tri-, and diphosphate (ATP, ADP) levels via luminometer, trypan blue exclusion and propidium iodide (PI) staining. Binding capacity of NK effector cells to target K-562 cells was also microscopically assessed. RESULTS: Thermal treatments between 37 and 41 degrees C did not significantly affect the ATP levels of NK cells. Between 41 degrees C and 42 degrees C, ATP levels significantly decreased, whilst there was an insignificant reduction up to 45 degrees C. At 42 degrees C or higher, no recovery was detectable. At 42 degrees C, the ATP level of NK cells rescued by IL-2 were significantly higher than those of controls at 37 degrees C. IFNalpha, beta and gamma had no significant effects. A combination of heating at 42 degrees C and irradiation at 20 Gy significantly reduced the ATP levels (p<0.001) more than heating and irradiation alone. At 42 degrees C, IL-2 abolished the reduction of ATP levels by heating and irradiation. This effect was dependent on heating time and irradiation dose. The ATP/ADP ratio did not significantly change when NK cells were heated for different times at 42 degrees C. Thermal treatment of target K-562 cells at temperatures from 37 to 45 degrees C reduced the number of NK cells binding K-652 cells. CONCLUSION: In vitro, NK cell viability was strongly reduced between 41 degrees C and 42 degrees C. At 42 degrees C, the combination of irradiation and thermal treatment reduced the ATP levels in NK cells. However, IL-2 restored cell viability depending on thermal and radiation doses. CI - Copyright(c) 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Hietanen, Tenho AU - Hietanen T AD - Department of Oncology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland tenho@hietanen.net. FAU - Kapanen, Mika AU - Kapanen M AD - Department of Oncology, Tampere University Hospital, Tampere, Finland. AD - Department of Medical Physics, Tampere University Hospital, Tampere, Finland. FAU - Kellokumpu-Lehtinen, Pirkko-Liisa AU - Kellokumpu-Lehtinen PL AD - Department of Oncology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. AD - Department of Oncology, Tampere University Hospital, Tampere, Finland. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Cytokines) RN - 0 (Interleukin-2) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Diphosphate/metabolism MH - Adenosine Triphosphate/metabolism MH - Cell Survival MH - Cells, Cultured MH - Cytokines/*pharmacology MH - Humans MH - Hyperthermia, Induced/*methods MH - Interleukin-2/pharmacology MH - K562 Cells MH - Killer Cells, Natural/physiology/*radiation effects MH - Radiotherapy/*methods OTO - NOTNLM OT - ADP OT - ATP OT - IFN OT - IL-2 OT - Natural killer (NK) cells OT - hyperthermia OT - irradiation OT - recovery OT - viability EDAT- 2018/01/29 06:00 MHDA- 2018/02/09 06:00 CRDT- 2018/01/29 06:00 PHST- 2017/11/01 00:00 [received] PHST- 2017/11/27 00:00 [revised] PHST- 2017/11/30 00:00 [accepted] PHST- 2018/01/29 06:00 [entrez] PHST- 2018/01/29 06:00 [pubmed] PHST- 2018/02/09 06:00 [medline] AID - 38/2/655 [pii] AID - 10.21873/anticanres.12269 [doi] PST - ppublish SO - Anticancer Res. 2018 Feb;38(2):655-663. doi: 10.21873/anticanres.12269.