Age-associated alterations of inflammatory and immune response, and oxidative stress in healthy and non-obese Koreans

Abstract

The objective of this study was 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 (8-epi-PGF2α). In total, 987 healthy and non-obese subjects was divided into five age groups: 20-34 (group 1, n=128), 35-44 (group 2, n=135), 45-54 (group 3, n=276), 55-64 (group 4, n=301), and 65-80 (group 5, n=147) years of age. After adjusted for body mass index, gender distribution, and smoking and drinking status, serum interferon (IFN)-γ levels decreased in group 3, 4 and 5 compared with those in group 1, and 2. Production of IFN-γ by the unstimulated PBMCs was lower in the older groups (group 4 and 5) than in the younger groups (group 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 group 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 effector cell: target cell=5:1 was positively affected by PBMC IFN-γ. Our study shows the age-related reductions in serum and PBMC IFN-γ and serum IL-12, and age-related increase in serum and PBMC IL-6 and oxidative stress in healthy non-obese subjects. Additionally, circulating IL-6 levels may be a better marker of a chronic low-grade inflammatory activity associated with aging than systemic levels of high-sensitivity C-reactive protein, tumor necrosis factor-α, and IL-1β.

노화가 진행되면 면역시스템의 이상조절로 인해서 만성적인 염증이 생기고 이것이 노인성 질환을 일으킨다. 본 연구에서는 면역과 관련된 INF-ɣ, PBMC production, IL-6, TNF-α 그리고 NK cell 활성 등이 연령에 따라 어떻게 변화하는지 살펴보았다. 987명의 건강한 정상체중의 성인에 대하여 BMI, 성별, 음주와 흡연 여부를 보정 후 나이를 기준으로 5개의 그룹: 20-34세 (group 1, N=128), 35-44세 (group 2, n=135), 45-54세 (group 3, n=276), 55-62세 (group 4, n=301), 65-90세 (group 5, n=147)으로 구분하였다. Serum INF-ɣ와 PBMC INF-ɣ는 고연령군에서 저연령군보다 낮은 수준으로 확인되었고 Serum IL-12도 고연령군에서 낮게 관찰되었다. 반면에Serum IL-6와 PBMC IL-6는 저연령군보다 고연령군에서 높게 관찰되었다. 또한 산화스트레스 수준을 반영하는 urinary 8-epi-PGF2α도 고연령군에서 높게 관찰되었으며 이들은 유의적인 차이를 보였다. 다중회귀분석 결과, PBMC IFN-ɣ는 NK cell 활성을 증가시키는 것으로 확인되었다. 결론적으로 건강한 정상체중의 성인에게서 연령에 따라 IFN-ɣ와 PBMC IFN-ɣ는 감소하는 경향이 있고 IL-6와 PBMC IL-6 그리고 산화스트레스는 증가하였다. 또한 만성적인 염증에 대해서는 전체적인 수준의 hs-CRP, TNF-α, IL-1β 보다 circulating IL-6 가 더 나은 지표일 수도 있다.