Glucocorticoids (GCs) are steroid hormones characterized by their anti-inflammatory and immunosuppressive nature. Although GCs are very commonly prescribed, in several diseases, including sepsis, their clinical treatment is hampered by side effects and by the occurrence of glucocorticoid resistance (GCR). Sepsis is defined as a life-threatening organ dysfunction, initiated by a dysregulated systemic host response to infections. With at least 19 million cases per year and a lethality rate of about 25%, sepsis is one of the most urgent unmet medical needs. The gut is critically affected during sepsis and is considered as a driving force in this disease. Despite there is no effective treatment for sepsis, pre-clinical studies show promising results by preserving or restoring gut integrity. Since GC treatment reveals therapeutic effects in Crohn's disease (CD) and in pre-clinical sepsis models, we hypothesize that targeting GCs to the gut or stimulating local GC production in the gut forms an interesting strategy for sepsis treatment. According to recent findings that show that dimerization of the glucocorticoid receptor (GR) is essential in inducing anti-inflammatory effects in pre-clinical sepsis models, we predict that new generation GCs that selectively dimerize the GR, can therefore positively affect the outcome of sepsis treatment.

中文翻译：

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糖皮质激素治疗败血症期间肠道炎症的潜力。

糖皮质激素 (GC) 是类固醇激素，其特征在于它们的抗炎和免疫抑制性质。尽管 GC 是非常普遍的处方，但在包括败血症在内的几种疾病中，它们的临床治疗受到副作用和糖皮质激素抵抗 (GCR) 的阻碍。脓毒症被定义为危及生命的器官功能障碍，由宿主对感染的失调全身反应引发。每年至少有 1900 万例病例和约 25% 的致死率，败血症是最紧迫的未满足的医疗需求之一。肠道在败血症期间受到严重影响，被认为是这种疾病的驱动力。尽管对败血症没有有效的治疗方法，但临床前研究通过保持或恢复肠道完整性显示出有希望的结果。由于 GC 治疗揭示了克罗恩的治疗效果 s 疾病 (CD) 和临床前脓毒症模型中，我们假设将 GC 靶向肠道或刺激肠道中的局部 GC 产生形成一种有趣的脓毒症治疗策略。根据最近的研究结果表明，糖皮质激素受体 (GR) 的二聚化对于在临床前脓毒症模型中诱导抗炎作用至关重要，我们预测，选择性二聚化 GR 的新一代 GC 可以因此对脓毒症的结果产生积极影响治疗。