Klawitter Jost, Clauw Andrew D, Seifert Jennifer A, Klawitter Jelena, Tompson Bridget, Sempio Cristina, Ingram Susan L, Christians Uwe, Moreland Larry W
Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Psychiatry, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Int J Mol Sci. 2025 Jun 14;26(12):5707. doi: 10.3390/ijms26125707.
Inflammation is a complicated physiological process that contributes to a variety of disorders including osteoarthritis (OA) and rheumatoid arthritis (RA). Endocannabinoids and the endocannabinoid system (ECS) play a pivotal role in the physiological response to pain and inflammation. A clinical study to investigate the role of the endocannabinoid system and related lipids in pain and inflammation in OA and RA was performed. In total, 80 subjects, namely, 25 patients with RA, 18 with OA, and 37 healthy participants, were included. Sixteen endocannabinoids and congeners, as well as 129 oxylipins, were quantified in plasma using specific, quantitative LC-MS/MS assays. The endocannabinoid analysis revealed significantly lower levels of 2-arachidonoylglycerol (2-AG) in RA and OA patients compared to healthy participants. In contrast, the EC levels of the ethanolamide group (anandamide, docosahexaenoyl-EA, palmitoleoyl-EA, and other ethanolamides) were higher in the RA study cohort and to a lesser extent also in the OA cohort. This analysis of oxylipins revealed lower levels of the pro-resolving lipid 9-oxo-octadecadienoic acid (9-oxoODE) and the ω-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in RA compared to all other study cohorts. 2-AG is a key regulator of nociception and inflammation, and its relatively low levels might be a mechanistic contributor to residual pain and inflammation in RA and OA. Several changes in pro- and anti-inflammatory lipid mediators were detected, including lower levels of EPA and DHA in RA, which might reveal the potential for nutritional supplementation with these anti-inflammatory fatty acids.
炎症是一个复杂的生理过程，与包括骨关节炎（OA）和类风湿关节炎（RA）在内的多种疾病有关。内源性大麻素和内源性大麻素系统（ECS）在对疼痛和炎症的生理反应中起关键作用。一项临床研究旨在调查内源性大麻素系统及相关脂质在OA和RA的疼痛与炎症中的作用。总共纳入了80名受试者，即25名RA患者、18名OA患者和37名健康参与者。使用特定的定量液相色谱-串联质谱（LC-MS/MS）分析法对血浆中的16种内源性大麻素及其类似物以及129种氧化脂质进行了定量分析。内源性大麻素分析显示，与健康参与者相比，RA和OA患者体内的2-花生四烯酸甘油酯（2-AG）水平显著降低。相比之下，乙醇酰胺组（花生四烯乙醇胺、二十二碳六烯酰乙醇胺、棕榈油酰乙醇胺和其他乙醇酰胺）的EC水平在RA研究队列中较高，在OA队列中也有一定程度的升高。对氧化脂质的分析显示，与所有其他研究队列相比，RA患者体内的促消退脂质9-氧代-十八碳二烯酸（9-氧代-十八碳二烯酸）以及ω-3脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）水平较低。2-AG是伤害感受和炎症的关键调节因子，其相对较低的水平可能是RA和OA残留疼痛和炎症的一个机制性因素。检测到促炎和抗炎脂质介质有多项变化，包括RA患者体内EPA和DHA水平较低，这可能揭示了用这些抗炎脂肪酸进行营养补充的潜力。
