Cytokine Antagonists in Aged Subjects and Their Relation With Cellular Immunity

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Abstract
Host responses to infectious and inflammatory stimuli are altered with aging. Because cytokines and their antagonists are significant factors in these host responses, the present research on aged subjects was designed to investigate plasma concentrations of the cytokines interleukin 7(3 (IL-1β) and tumor necrosis factor a (TNFα) and those of their antagonists IL-1 receptor antagonist (IL-lra) and soluble TNF receptor (sTNFr). For this research, 122 apparently healthy aged subjects (79.6 ± 5.8 yr), 39 aged individuals with documented urinary tract infections (UTIs) (81.6 ± 6.3 yr), and 100young controls (39.32 ± 11.2 yr) were included. Plasma IL-1 0, TNFa, IL-lra, sTNFr (55 kDa), and neopterin were measured using enzyme-linked immunosorbent assay techniques. In subsets of normal aged subjects and UTI patients, we investigated relations between plasma concentrations of cytokine antagonists and IL-2 production by phytohemagglutinin-stimulated peripheral blood mononuclear cells. The results show that plasma concentrations of both IL-lra and sTNFr were greater in healthy aged subjects than in young controls. Plasma neopterin, a product of activated monocyteslmacrophages, was likewise elevated in the aged. IL-1 and TNF were not detectable in the majority of plasma samples. There was a positive correlation between neopterin concentration and both IL-lra and sTNFr. There was a significant negative correlation between plasma IL-lra and IL-2 production by phytohemagglutinin-stimulated peripheral blood mononuclear cell in healthy aged subjects. IL-lra and sTNFr concentrations were significantly greater in patients with UTI than in the healthy aged subjects. In UTI patients IL-2 production in vitro was lower than in healthy subjects, but there was no significant correlation with IL-lra in plasma. Therefore, plasma concentrations of cytokine antagonists are increased in plasma of apparently healthy aged subjects. Elevated concentrations of neopterin suggest that this increase can be traced to monocyte activation. The negative correlation between plasma IL-lra and IL-2 production in vitro suggests that enhancement of this cytokine antagonist can contribute to immunodepression of aging. We propose that unapparent infections in aged subjects cause monocyte activation and release of cytokine antagonists. These cytokine antagonists reduce IL-2 production and the capability of T cells to proliferate, thereby inhibiting immune responses in the elderly.

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