Introduction: Seasonal changes influence the immune response, and vitamin D deficiency is commonly observed in winter due to reduced ultraviolet (UV) radiation. Low-dose UV radiation is known to enhance the activation of both innate and adaptive immune cells. Natural killer (NK) cell immunotherapy is gaining attention, yet the seasonal variation in interferon-gamma (IFN-γ) secretion by NK cells remains understudied.

Methods: NK cell activity was assessed by measuring the concentration of IFN-γ after stimulation with NK cell-specific stimulants (NK Vue, NK Max, Sungnam, Korea). Data from NK cell activity tests conducted on individuals visiting the Health Checkup Center at Dong-A University Hospital from 2018 to 2023 were analyzed. Four seasonal periods—January-February, April-May, July-August, and October-November—were selected, and the mean of NK cell activity was calculated for each season.

Results: A total of 4,726 tests were performed over a 48-month period. The mean age of participants was 59.7±11.0 years, with a male-to-female ratio of 1:0.84. Seasonal variations in mean NK cell activity were statistically significant (p < 0.0001 by Chi-squared test). NK cell activity was highest in winter, followed by fall, summer, and spring. A statistically significant difference was observed between winter and spring (1235.8 pg/mL vs. 1143.6 pg/mL, p = 0.017).

Conclusion: IFN-γ secretion by NK cells exhibited seasonal variation, with the highest levels in winter. Further research on the seasonal variation in NK cell function is warranted. Consideration of this variation should be incorporated into immunotherapy strategies and basic research.