Archives of Obesity and Metabolism (비만대사연구학술지)

The Study of Obesity and Metabolic Syndrome, KAFM (대한가정의학회 비만대사증후군연구회)
권호 표지
DOI QR코드

DOI QR Code

Association Between White Blood Cell Count and NK Cell Activity and Effect Modification by Abdominal Obesity: A Cross-Sectional Study in a Health Screening Cohort

백혈구 수와 NK 세포 활성도 간의 연관성 및 복부비만의 효과 수정: 건강검진 코호트 기반 단면연구

  • Jooheun Kim (Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • Ji-Won Lee (Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • Yaeji Lee (Department of Biomedical Systems Informatics, Yonsei University College of Medicine) ;
  • Yu-Jin Kwon (Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine)
  • 김주흔 (연세대학교 의과대학 세브란스병원 가정의학과) ;
  • 이지원 (연세대학교 의과대학 세브란스병원 가정의학과) ;
  • 이예지 (연세대학교 의과대학 의생명시스템정보학교실) ;
  • 권유진 (연세대학교 의과대학 세브란스병원 가정의학과)
  • Received : 2026.04.30
  • Accepted : 2026.06.02
  • Published : 2026.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: White blood cell (WBC) count is a widely used marker of systemic inflammation. Chronic low-grade inflammation has been implicated in impaired natural killer (NK) cell function. However, factors modifying this relationship remain unclear. Because abdominal obesity is associated with chronic inflammation, it may be a key modifier. This study examined whether abdominal obesity modifies the association between WBC count and NK cell activity. Methods: This cross-sectional, single-center study included 1,646 adults who underwent health examinations at Yongin Severance Hospital, Korea (2017-2024). NK cell activity was measured using the NK Vue® Kit. Abdominal obesity was defined as waist circumference ≥90 cm in men and ≥85 cm in women. Multivariable logistic regression analysis was performed, adjusting for age, sex, and body mass index (BMI). Restricted cubic spline analysis was used to assess the dose-response relationship. Effect modification was evaluated using interaction terms (P for interaction <0.10). Results: Higher WBC count was associated with low NK cell activity (odds ratio [OR] 1.25, P<0.001), with a monotonically increasing dose-response relationship (P for nonlinearity = 0.689). In stratified analyses, the association was stronger in the non-abdominal obesity group (Q4 OR 2.73, P<0.001) than in the abdominal obesity group (Q4 OR 2.14, P = 0.030), with evidence of interaction (P for interaction = 0.096). BMI-defined obesity showed no significant interaction (P = 0.496). Conclusion: Higher WBC count was associated with low NK cell activity in a health screening cohort. This association was attenuated in individuals with abdominal obesity, suggesting that abdominal obesity may modify the relationship between systemic inflammation and NK cell function.

Keywords

References

  1. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol 2008;9:503-10. https://doi.org/10.1038/ni1582
  2. Chiossone L, Dumas PY, Vienne M, Vivier E. Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol 2018;18:671-88. https://doi.org/10.1038/s41577-018-0061-z
  3. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 2000;356:1795-9. https://doi.org/10.1016/S0140-6736(00)03231-1
  4. Lee J, Park KH, Ryu JH, et al. Natural killer cell activity for IFN-gamma production as a supportive diagnostic marker for gastric cancer. Oncotarget 2017;8:70431-40. https://doi.org/10.18632/oncotarget.v8i41
  5. Takeuchi H, Maehara Y, Tokunaga E, Koga T, Kakeji Y, Sugimachi K. Prognostic significance of natural killer cell activity in patients with gastric carcinoma: a multivariate analysis. Am J Gastroenterol 2001;96:574-8. https://doi.org/10.1111/j.1572-0241.2001.03535.x
  6. Lee SB, Cha J, Kim IK, et al. A high-throughput assay of NK cell activity in whole blood and its clinical application. Biochem Biophys Res Commun 2014;445:584-90. https://doi.org/10.1016/j.bbrc.2014.02.040
  7. Nederby L, Jakobsen A, Hokland M, Hansen TF. Quantification of NK cell activity using whole blood: methodological aspects of a new test. J Immunol Methods 2018;458:21-5. https://doi.org/10.1016/j.jim.2018.04.002
  8. Kim BR, Chun S, Cho D, Kim KH. Association of neutrophil-to-lymphocyte ratio and natural killer cell activity revealed by measurement of interferon-gamma levels in a healthy population. J Clin Lab Anal 2019;33:e22640. https://doi.org/10.1002/jcla.2019.33.issue-1
  9. Lee YK, Haam JH, Cho SH, Kim YS. Cross-sectional and time-dependent analyses on inflammatory markers following natural killer cell activity. Diagnostics (Basel) 2022;12:448. https://doi.org/10.3390/diagnostics12020448
  10. Cho AR, Oh H, Suh E, et al. Association between complete blood cell count (CBC)-derived inflammatory markers and natural killer cell activity: a cross-sectional study. J Inflamm Res 2026;19:557260. https://doi.org/10.2147/JIR.S557260
  11. Margolis KL, Manson JE, Greenland P, et al. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study. Arch Intern Med 2005;165:500-8. https://doi.org/10.1001/archinte.165.5.500
  12. Margolis KL, Rodabough RJ, Thomson CA, Lopez AM, McTiernan A. Prospective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal women. Arch Intern Med 2007;167:1837-44. https://doi.org/10.1001/archinte.167.17.1837
  13. Huang ZS, Chien KL, Yang CY, Tsai KS, Wang CH. Peripheral differential leukocyte counts in humans vary with hyperlipidemia, smoking, and body mass index. Lipids 2001;36:237-45. https://doi.org/10.1007/s11745-001-0713-9
  14. Jung CH, Lee WY, Kim BY, et al. The risk of metabolic syndrome according to the white blood cell count in apparently healthy Korean adults. Yonsei Med J 2013;54:615-20. https://doi.org/10.3349/ymj.2013.54.3.615
  15. Bähr I, Spielmann J, Quandt D, Kielstein H. Obesity-associated alterations of natural killer cells and immunosurveillance of cancer. Front Immunol 2020;11:245. https://doi.org/10.3389/fimmu.2020.00245
  16. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013;2013:139239. https://doi.org/10.1155/2013/139239
  17. Michelet X, Dyck L, Hogan A, et al. Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol 2018;19:1330-40. https://doi.org/10.1038/s41590-018-0251-7
  18. Lynch LA, O'Connell JM, Kwasnik AK, Cawood TJ, O'Farrelly C, O'Shea DB. Are natural killer cells protecting the metabolically healthy obese patient? Obesity (Silver Spring) 2009;17:601-5. https://doi.org/10.1038/oby.2008.565
  19. Janssen I, Katzmarzyk PT, Ross R. Waist circumference and not body mass index explains obesity-related health risk. Am J Clin Nutr 2004;79:379-84. https://doi.org/10.1093/ajcn/79.3.379
  20. Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006;444:881-7. https://doi.org/10.1038/nature05488
  21. Oh S, Chun S, Hwang S, et al. Vitamin D and exercise are major determinants of natural killer cell activity, which is age- and gender-specific. Front Immunol 2021;12:594356. https://doi.org/10.3389/fimmu.2021.594356
  22. Brookes ST, Whitely E, Egger M, Smith GD, Mulheran PA, Peters TJ. Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test. J Clin Epidemiol 2004;57:229-36. https://doi.org/10.1016/j.jclinepi.2003.08.009
  23. Steffen BT, Thanassoulis G, Duprez D, et al. Race-based differences in lipoprotein(a)-associated risk of carotid atherosclerosis. Arterioscler Thromb Vasc Biol 2019;39:523-9. https://doi.org/10.1161/ATVBAHA.118.312267
  24. Costantini C, Cassatella MA. The defensive alliance between neutrophils and NK cells as a novel arm of innate immunity. J Leukoc Biol 2011;89:221-33. https://doi.org/10.1189/jlb.0510250
  25. Palano MT, Gallazzi M, Cucchiara M, et al. Neutrophil and natural killer cell interactions in cancers: dangerous liaisons instructing immunosuppression and angiogenesis. Vaccines (Basel) 2021;9:1488. https://doi.org/10.3390/vaccines9121488
  26. Jia H, Yang H, Xiong H, Luo KQ. NK cell exhaustion in the tumor microenvironment. Front Immunol 2023;14:1303605. https://doi.org/10.3389/fimmu.2023.1303605
  27. Bähr I, Goritz V, Doberstein H, et al. Diet-induced obesity is associated with an impaired NK cell function and an increased colon cancer incidence. J Nutr Metab 2017;2017:4297025. https://doi.org/10.1155/2017/4297025
  28. Bähr I, Jahn J, Zipprich A, Pahlow I, Spielmann J, Kielstein H. Impaired natural killer cell subset phenotypes in human obesity. Immunol Res 2018;66:234-44. https://doi.org/10.1007/s12026-018-8989-4
  29. Wouters K, Kusters YHAM, Bijnen M, et al. NK cells in human visceral adipose tissue contribute to obesity-associated insulin resistance through low-grade inflammation. Clin Transl Med 2020;10:e192. https://doi.org/10.1002/ctm2.v10.6
  30. Cho AR, Suh E, Oh H, Cho BH, Gil M, Lee YK. Low muscle and high fat percentages are associated with low natural killer cell activity: a cross-sectional study. Int J Mol Sci 2023;24:12505. https://doi.org/10.3390/ijms241512505
  31. Jung YS, Park JH, Park DI, Sohn CI, Lee JM, Kim TI. Physical inactivity and unhealthy metabolic status are associated with decreased natural killer cell activity. Yonsei Med J 2018;59:554-62. https://doi.org/10.3349/ymj.2018.59.4.554
  32. Jung YS, Park JH, Park DI, Sohn CI, Lee JM, Kim TI. Impact of smoking on human natural killer cell activity: a large cohort study. J Cancer Prev 2020;25:13-20. https://doi.org/10.15430/JCP.2020.25.1.13
  33. Nakachi K, Imai K. Environmental and physiological influences on human natural killer cell activity in relation to good health practices. Jpn J Cancer Res 1992;83:798-805. https://doi.org/10.1111/cas.1992.83.issue-8
  34. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99. https://doi.org/10.1016/j.cell.2010.01.025
  35. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454:436-44. https://doi.org/10.1038/nature07205
  36. Irwin M, Mascovich A, Gillin JC, Willoughby R, Pike J, Smith TL. Partial sleep deprivation reduces natural killer cell activity in humans. Psychosom Med 1994;56:493-8. https://doi.org/10.1097/00006842-199411000-00004
  37. Villageliu DN, Cunningham KC, Smith DR, et al. Natural killer cell effector function is critical for host defense against alcohol-associated bacterial pneumonia. NPJ Biofilms Microbiomes 2024;10:79. https://doi.org/10.1038/s41522-024-00558-w
  38. Vitale C, Chiossone L, Cantoni C, et al. The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicity. Eur J Immunol 2004;34:3028-38. https://doi.org/10.1002/eji.v34:11
  39. Yang Y, Day J, Souza-Fonseca Guimaraes F, Wicks IP, Louis C. Natural killer cells in inflammatory autoimmune diseases. Clin Transl Immunology 2021;10:e1250. https://doi.org/10.1002/cti2.v10.2