Impact of Age and Gender on Serum Cytokine and Chemokine Levels: Analysis of 157 Healthy Subjects across Consecutive Age Groups.

INTRODUCTION

Understanding the effects of age and sex on circulating cytokine and chemokine levels in healthy individuals is essential for establishing reliable reference ranges and tailoring assessments. Although previous studies have compared younger and older populations, few have systematically examined sequential age decades. This study aimed to characterize continuous age-related changes in serum cytokine and chemokine profiles across adulthood in 157 healthy individuals.

METHODS

Serum samples from 100 individuals aged 20s-60s (10 males and 10 females per decade) were obtained from the Japanese Red Cross Society. Additional samples from 57 individuals aged 60s-80s (17-20 per decade) were included. Concentrations of 26 cytokines and chemokines were measured using a multiplex bead-based immunoassay. Associations between analyte levels and age were assessed using the Jonckheere test and Spearman's rank correlation. Sex differences were evaluated using Student's t test. A two-sided p value <0.05 was considered statistically significant.

RESULTS

Three distinct age-related patterns were identified. Type 1 demonstrated continuous trends from the 20s to the 80s: interleukin (IL)-2, IP-10, thymus and activation-regulated chemokine, and granulysin increased significantly with age, whereas TGF-β, fibroblast growth factor-2, and fractalkine decreased significantly. Type 2a (interferon-γ, IL-17, and IL-15) showed significant declines from the 20s to the 60s but an overall increase from the 20s to the 80s. Type 2b included IL-12p70, tumor necrosis factor-α, IL-10, IL-5, and IL-7, which increased significantly from the 20s to the 80s, and IL-8, which decreased; however, no significant trends were observed between the 20s and 60s. Type 2c (IL-6 and IL-1Ra) increased significantly from the 20s to the 60s but showed no significant trend across the 20s-80s. Between the 20s and 60s, IL-15, IL-1Ra, TGF-β, and IP-10 were significantly higher in females, whereas IL-8 and granulysin were higher in males. Across the 20s-80s, only IL-1Ra and TGF-β remained higher in females, and IL-8 remained higher in males.

CONCLUSION

Certain cytokines exhibited consistent age- and gender-related trends, whereas others varied between the 20s-60s and the 20s-80s.