RESUMO
OBJECTIVE: Oxylipins are bioactive lipids derived from polyunsaturated fatty acids (PUFAs) that modulate inflammation and may remain overexpressed in refractory synovitis. In plasma, they could also be biomarkers of synovial pathology. The aim of this study is to determine if synovial oxylipins in inflamed joints correlate with plasma oxylipins and with synovial histologic patterns. METHODS: Patients with established rheumatoid or psoriatic arthritis with active disease despite treatment were recruited, and paired synovial tissue (ST) and plasma were collected. Oxylipins were determined by liquid chromatography with tandem mass spectrometry and were classified into groups according to their PUFA precursor and enzyme. The expression of CD20, CD68, CD3, and CD138 was obtained to describe synovial histology. Cell-specific expression of oxylipin-related genes was identified by examining available synovial single-cell RNA sequencing data. RESULTS: We included a total of 32 ST and 26 paired-plasma samples. A total of 71 oxylipins were identified in ST, but only 24 were identified in plasma. Only levels of 9,10-dihydroxyoctadecenoic acid and tetranor-Prostaglandin FM had a significant positive correlation between plasma and ST. Several oxylipins and oxylipin-related genes were differentially expressed among synovial phenotypes. Specifically, several 5-lipoxygenase (LOX)-derived oxylipins were statistically elevated in the lympho-myeloid phenotype and associated with B cell expression in rheumatoid arthritis samples. CONCLUSION: The lack of correlation between ST and plasma oxylipins suggests that ST lipid profiling better characterizes active pathways in treated joints. Synovial 5-LOX-derived oxylipins were highly expressed in lympho-myeloid-enriched synovium. Combination therapy with 5-LOX inhibitors to improve refractory inflammation may be needed in patients with this histologic group.
Assuntos
Araquidonato 5-Lipoxigenase , Artrite Psoriásica , Artrite Reumatoide , Oxilipinas , Membrana Sinovial , Humanos , Membrana Sinovial/metabolismo , Oxilipinas/metabolismo , Artrite Reumatoide/metabolismo , Araquidonato 5-Lipoxigenase/metabolismo , Araquidonato 5-Lipoxigenase/genética , Pessoa de Meia-Idade , Masculino , Feminino , Artrite Psoriásica/metabolismo , Artrite Psoriásica/tratamento farmacológico , Ácidos Graxos Insaturados/metabolismo , Idoso , Adulto , Biomarcadores/metabolismoRESUMO
Objective: Rheumatic diseases result in chronic pain (CP) and require treatment with drugs whose prolonged administration is associated with side effects. However, publications in the academic literature have suggested that diet modification and food supplementation can play a crucial role in alleviating the symptoms of inflammatory disease. Thus, it is hoped that the use of an anti-inflammatory diet for pain management might result in improved quality of life. Hence, here we aimed to investigate the effect of anti-inflammatory foods in patients with CP caused by rheumatic diseases. Methods: After an exhaustive bibliography search, we designed a 13-item anti-inflammatory dietary guide based on a Mediterranean diet without red meat, gluten, or cow's milk (the AnMeD-S). We then conducted a pilot study to evaluate the efficacy of this anti-inflammatory diet in patients with CP. A food consumption score (with a maximum of 156 points) was then applied to evaluate patient adhesion to the proposed diet. Forty-five patients with CP were followed-up for 4 months. Variables related with quality of life (including pain perception, depression status, and sleep satisfaction) were measured using 9 validated questionnaires and anthropometric measurements were recorded before and after the participants followed the anti-inflammatory diet. Results: We found a correlation between increased anti-inflammatory food intake and improved physical characteristics, stress, and pain in the patients we assessed. Moreover, decreased consumption of pro-inflammatory foods was positively correlated with sleep satisfaction. Following the AnMeD-S was associated with improved physical characteristics and quality-of-life in patients with CP. Conclusion: The AnMeD-S, includes anti-inflammatory foods and restricts the consumption of certain pro-inflammatory foods (such as those containing gluten). This dietary pattern could provide relief from CP and improve the symptoms of stress and depression, as well as reducing sleep disturbances.