Catania A, Airaghi L, Motta P, Manfredi M G, Annoni G, Pettenati C, Brambilla F, Lipton J M
Third Division of Internal Medicine, IRCCS Ospedale Maggiore di Milano, Italy.
J Gerontol A Biol Sci Med Sci. 1997 Mar;52(2):B93-7. doi: 10.1093/gerona/52a.2.b93.
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 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) and those of their antagonists IL-1 receptor antagonist (IL-1ra) 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 100 young controls (39.32 +/- 11.2 yr) were included. Plasma IL-1 beta, TNF alpha, IL-1ra, 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-1ra and sTNFr were greater in healthy aged subjects than in young controls. Plasma neopterin, a product of activated monocytes/macrophages, 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-1ra and sTNFr. There was a significant negative correlation between plasma IL-1ra and IL-2 production by phytohemagglutinin-stimulated peripheral blood mononuclear cell in healthy aged subjects. IL-1ra 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-1ra 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-1ra 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 responses in the elderly.
宿主对感染性和炎症性刺激的反应会随着年龄增长而发生改变。由于细胞因子及其拮抗剂是这些宿主反应中的重要因素，因此本项针对老年受试者的研究旨在调查细胞因子白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNFα）及其拮抗剂IL-1受体拮抗剂（IL-1ra）和可溶性TNF受体（sTNFr）的血浆浓度。在本研究中，纳入了122名表面健康的老年受试者（79.6±5.8岁）、39名有记录的尿路感染（UTI）老年个体（81.6±6.3岁）和100名年轻对照者（39.32±11.2岁）。使用酶联免疫吸附测定技术测量血浆IL-1β、TNFα、IL-1ra、sTNFr（55 kDa）和新蝶呤。在正常老年受试者和UTI患者的亚组中，我们研究了细胞因子拮抗剂血浆浓度与植物血凝素刺激的外周血单个核细胞产生IL-2之间的关系。结果显示，健康老年受试者血浆中IL-1ra和sTNFr的浓度均高于年轻对照者。血浆新蝶呤是活化单核细胞/巨噬细胞的产物，在老年人中同样升高。大多数血浆样本中检测不到IL-1和TNF。新蝶呤浓度与IL-1ra和sTNFr均呈正相关。在健康老年受试者中，血浆IL-1ra与植物血凝素刺激的外周血单个核细胞产生IL-2之间存在显著负相关。UTI患者的IL-1ra和sTNFr浓度显著高于健康老年受试者。在UTI患者中，体外IL-2产生低于健康受试者，但与血浆中的IL-1ra无显著相关性。因此，在表面健康的老年受试者血浆中，细胞因子拮抗剂的血浆浓度升高。新蝶呤浓度升高表明这种升高可追溯到单核细胞活化。血浆IL-1ra与体外IL-2产生之间的负相关表明，这种细胞因子拮抗剂的增强可能导致衰老的免疫抑制。我们提出，老年受试者中的隐匿性感染会导致单核细胞活化并释放细胞因子拮抗剂。这些细胞因子拮抗剂会减少IL-2的产生以及T细胞增殖的能力，从而抑制老年人的反应。
