Barber A E, Coyle S M, Fischer E, Smith C, van der Poll T, Shires G T, Lowry S F
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Surgery. 1995 Aug;118(2):406-10; discussion 410-1. doi: 10.1016/s0039-6060(05)80352-6.
We have previously reported that the antecedent administration of glucocorticoids altered both the hormonal and proinflammatory cytokine responses to lipopolysaccharide (LPS) when administered to human volunteers. In that study, subjects with vastly exaggerated levels of tumor necrosis factor (TNF) and interleukin (IL)-6 12 and 144 hours after cortisol infusion exhibited hemodynamic and hormonal responses no different from those of untreated subjects after endotoxin. The current study examined levels of the antiinflammatory cytokines interleukin-1 receptor antagonist (IL-1ra) and soluble receptors to tumor necrosis factor (sTNF-R) in the same setting of the previous report.
Hydrocortisone succinate was infused into healthy volunteers. LPS was then injected immediately or was delayed by 6, 12, or 144 hours (C, C-6, C-12, and C-144, respectively). Subjects receiving LPS alone served as controls. Plasma was analyzed to determine levels of TNF, sTNF-R and IL-1ra by enzyme-linked immunosorbent assay before administration of LPS and at 30-minute intervals after administration of LPS for 6 hours.
Levels of sTNF-R increased after LPS administration in all groups (p < 0.05 versus baseline) with a significantly higher level recorded in the subjects having received hydrocortisone 144 hours before (C-144, p < 0.05 versus all other groups). TNF levels remained undetectable in association with immediate infusion of LPS (C) and the relatively short delay group (C6). This cytokine peaked 90 minutes after LPS in all other groups, with a significantly higher peak in the C-144 subjects when compared with controls. IL-1ra levels rose in all groups but to a lesser extent in the C group (p < 0.05).
These data confirm that glucocorticoids influence the production of both sTNF-R and IL-1ra. The potential for an exaggerated response of sTNF-R exists for an extended period of time after exposure to glucocorticoids.
我们之前报道过，给人类志愿者注射糖皮质激素后，再给予脂多糖（LPS），糖皮质激素的预先给药会改变激素和促炎细胞因子对LPS的反应。在该研究中，在注入皮质醇后12小时和144小时肿瘤坏死因子（TNF）和白细胞介素（IL）-6水平大幅升高的受试者，其血流动力学和激素反应与内毒素处理后未治疗的受试者无异。本研究在之前报告的相同背景下，检测了抗炎细胞因子白细胞介素-1受体拮抗剂（IL-1ra）和肿瘤坏死因子可溶性受体（sTNF-R）的水平。
将琥珀酸氢化可的松注入健康志愿者体内。然后立即注射LPS或延迟6、12或144小时（分别为C、C-6、C-12和C-144）。仅接受LPS的受试者作为对照。在给予LPS前以及给予LPS后6小时内每隔30分钟，通过酶联免疫吸附测定法分析血浆，以确定TNF、sTNF-R和IL-1ra的水平。
所有组在给予LPS后sTNF-R水平均升高（与基线相比，p < 0.05），在144小时前接受氢化可的松的受试者中记录到显著更高的水平（C-144，与所有其他组相比，p < 0.05）。与立即注入LPS（C）和延迟相对较短的组（C6）相关，TNF水平仍未检测到。在所有其他组中，该细胞因子在LPS后90分钟达到峰值，与对照组相比，C-144受试者的峰值显著更高。所有组中IL-1ra水平均升高，但C组升高程度较小（p < 0.05）。
这些数据证实糖皮质激素会影响sTNF-R和IL-1ra的产生。接触糖皮质激素后，sTNF-R存在长时间过度反应的可能性。
