Fratto Melanie A, Hart Kelsey A, Norton Natalie A, Barton Michelle H, Giguère Steeve, Hurley David J
Department of Large Animal Medicine, University of Georgia College of Veterinary Medicine, 2200 College Station Road, Athens, GA 30602.
Department of Large Animal Medicine, University of Georgia College of Veterinary Medicine, 2200 College Station Road, Athens, GA 30602.
Vet Immunol Immunopathol. 2017 Jan;183:16-21. doi: 10.1016/j.vetimm.2016.11.003. Epub 2016 Nov 18.
Cortisol is a key anti-inflammatory hormone that increases in bacterial sepsis and circulates predominantly bound to cortisol binding globulin (CBG). Only unbound cortisol was believed to be biologically active, but recent evidence suggests that CBG-bound cortisol also regulates inflammation. The objective of this study was to evaluate the effects of free and CBG-bound cortisol on equine neutrophil function ex vivo. We hypothesized that CBG would enhance cortisol-mediated suppression of neutrophil pro-inflammatory responses. Neutrophils isolated from 8 foals and 6 adult horses were exposed to Staphylococcus aureus antigen (SAA) alone and with hydrocortisone (HC), CBG, or both (CBG+HC). Inflammatory cytokine (TNF-α, IL-8) and reactive oxygen species (ROS) production were measured and compared among stimulants and between ages with linear mixed-effects models. CBG and CBG+HC inhibited ROS production induced by SAA in both foal and horse neutrophils, maintaining it at levels comparable to baseline production (P≤0.060-0.907). TNF-α production was not significantly different among stimulants (P=0.284). CBG+HC significantly (P≤0.016) increased IL-8 production by neutrophils in response to SAA in both foals and adults, although the response of foals was significantly greater than that of adults (P<0.001). These findings suggest that CBG directly modulates equine neutrophil responses, but the effects are cytokine- and age-specific.
皮质醇是一种关键的抗炎激素，在细菌性败血症中会升高，且主要以与皮质醇结合球蛋白（CBG）结合的形式在血液循环。过去认为只有未结合的皮质醇具有生物活性，但最近的证据表明，与CBG结合的皮质醇也能调节炎症。本研究的目的是在体外评估游离型和与CBG结合型皮质醇对马中性粒细胞功能的影响。我们假设CBG会增强皮质醇介导的对中性粒细胞促炎反应的抑制作用。从8匹幼驹和6匹成年马中分离出的中性粒细胞，分别单独暴露于金黄色葡萄球菌抗原（SAA）以及与氢化可的松（HC）、CBG或两者（CBG + HC）共同暴露。使用线性混合效应模型测量并比较了不同刺激物之间以及不同年龄组之间的炎性细胞因子（TNF-α、IL-8）和活性氧（ROS）的产生情况。CBG和CBG + HC均抑制了幼驹和成年马中性粒细胞中由SAA诱导的ROS产生，使其维持在与基线产生水平相当的水平（P≤0.060 - 0.907）。不同刺激物之间的TNF-α产生没有显著差异（P = 0.284）。CBG + HC显著（P≤0.016）增加了幼驹和成年马中性粒细胞对SAA刺激产生的IL-8，尽管幼驹的反应显著大于成年马（P < 0.001）。这些发现表明，CBG直接调节马中性粒细胞的反应，但作用具有细胞因子和年龄特异性。
