Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-FFCLRP, Universidade de São Paulo-USP, Ribeirao Preto 14040-901, SP, Brazil.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-FCFRP, Universidade de São Paulo-USP, Ribeirao Preto 14040-903, SP, Brazil.
Viruses. 2023 Feb 19;15(2):573. doi: 10.3390/v15020573.
COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients ( = 200) and healthy controls ( = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.
新型冠状病毒病（COVID-19）与免疫失调有关。目前，有几种药物被批准用于治疗这种疾病。由于它们在抑制促炎细胞因子和脂质介质方面的重要作用，糖皮质激素（GCs）引起了广泛关注。同样，内源性大麻素（eCB）系统调节包括免疫反应在内的各种生理过程。此外，在炎症和血栓形成过程中，细胞膜中的磷脂被裂解以产生血小板激活因子（PAF），这也是一种脂质介质。然而，GC 在 COVID-19 治疗期间对这条脂质途径的影响尚不清楚。这是一项涉及 COVID-19 患者（n = 200）和健康对照者（n = 35）的横断面研究。对血浆脂质介质的靶向串联质谱分析表明，COVID-19 的严重程度影响了 eCB 和 PAF 的合成。这种 eCB 的合成增加与全身炎症标志物 IL-6 和可溶性髓系细胞触发受体-1（sTREM-1）水平和中性粒细胞计数呈负相关。GC 的使用通过降低 PAF 和增加 2-AG 的产生来改变这些脂质途径。对 GC 治疗患者血液白细胞的转录组分析表明，单酰基甘油脂肪酶和磷脂酶 A2 基因表达的差异调节。总的来说，这些发现为我们对 COVID-19 病理生理学的理解提供了突破，表明 GC 可能通过影响疾病进程中涉及的 eCB 和 PAF 途径来促进额外的保护药理学作用。
