Aging is associated with circulating cytokine dysregulation

Purpose: Aging is accompanied by a progressive increase in pro-inflammatory cytokine status. However, little is known about the development of age-dependent modifications in other circulating cytokines. The aim of this study was to investigate in vivo the influence of age on circulating cytokine production in healthy subjects (HC). Methods: Circulating cytokines were measured by CBA and ELISA in 73 HC. Intracellular cytokine production was assessed in CD3+ and CD14+ cells by flow cytometry. Production of cytokines in cell culture supernatants was also studied after polyclonal stimulation. Results: Subjects were divided into three different groups according to age: 28 young HC (<30 years, 26.2 +/- 2.4), 24 middle age HC (30-60 years, 44.7 +/- 8.4) and 21 elderly HC (>60 years, 70.6 +/- 7.9). Age was positively correlated with the circulating levels of IL-12p70, IL-1 beta, TNF alpha, IL-6, and IL-10. Age had a negative correlation with circulating levels of IL-17. Besides, age was positively correlated with spontaneous intracellular expression of proinflammatory cytokines in circulating monocytes. No correlation was found with other intracellular cytokine expression or with the production of cytokines in cell culture supernatants after in vitro stimulation. Gender had a marginal effect on the circulating cytokine profile. Conclusion: Aging has a significant impact on the production of circulating cytokines in healthy individuals. The circulating cytokine milieu may contribute to the development of age-restricted conditions. (C) 2012 Elsevier Inc. All rights reserved.