This study aimed to determine age-dependent alterations in serum cytokines, peripheral blood mononuclear cell (PBMC) cytokine production, natural killer (NK) cell activity, and urinary 8-epi-prostaglandin F2α (PGF2α). Nine hundred eighty-seven healthy and nonobese subjects were divided into five age groups: 20–34 (group 1), 35–44 (group 2), 45–54 (group 3), 55–64 (group 4), and 65–80 (group 5) years of age. After adjusting for BMI, sex, and smoking and drinking status, serum interferon (IFN)-γ levels decreased in groups 3, 4, and 5 compared with those in groups 1 and 2. Production of IFN-γ by unstimulated PBMCs was lower in the older groups (groups 4 and 5) than in the younger groups (groups 1 and 3). Serum interleukin (IL)-12 was lower in group 5 than in groups 1 and 2. In contrast, both serum and PBMC IL-6 were higher in group 5 than in groups 1, 2, and 3. Urinary 8-epi-PGF2α increased in group 3 compared with that in group 1 and further increased in group 5. Multiple linear regression analysis revealed that serum IFN-γ levels were negatively affected by age, and NK cell activity at a ratio of E:T = 5:1 was positively affected by PBMC IFN-γ. This study shows the age-related reductions in serum and PBMC IFN-γ and serum IL-12 and age-related increases in serum and PBMC IL-6 and oxidative stress in healthy nonobese subjects. Additionally, circulating IL-6 levels may be a better marker of the chronic low-grade inflammatory activity associated with aging than systemic levels of high-sensitivity C-reactive protein, TNF-α, and IL-1β.
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