Glucocorticoids (GCs) are endogenous hormones that are crucial for the homeostasis of the organism and adaptation to the external environment. Because of their anti-inflammatory effects, synthetic GCs are also extensively used in clinical practice. However, almost all cells in the body are sensitive to GC regulation. As a result, these mediators have pleiotropic effects, which may be undesirable or detrimental to human health. Here, we summarize the recent findings that contribute to deciphering the molecular mechanisms downstream of glucocorticoid receptor activation. We also discuss the complex role of GCs in infectious diseases such as sepsis and COVID-19, in which the balance between pathogen elimination and protection against excessive inflammation and immunopathology needs to be tightly regulated. An understanding of the cell type- and context-specific actions of GCs from the molecular to the organismal level would help to optimize their therapeutic use.

糖皮质激素 (GCs) 是内源性激素，对机体的稳态和对外部环境的适应至关重要。由于它们的抗炎作用，合成的 GCs 也广泛用于临床实践。然而，体内几乎所有的细胞都对 GC 调节敏感。因此，这些介质具有多效性，可能对人类健康不利或有害。在这里，我们总结了有助于破译糖皮质激素受体激活下游分子机制的最新发现。我们还讨论了 GC 在败血症和 COVID-19 等传染病中的复杂作用，其中需要严格调节病原体消除与防止过度炎症和免疫病理学之间的平衡。