Harnessing Inflammation Resolution in Arthritis: Current Understanding of Specialized Pro-resolving Lipid Mediators’ Contribution to Arthritis Physiopathology and Future Perspectives

Abstract

The concept behind the resolution of inflammation has changed in the past decades from a passive to an active process, which reflects in novel avenues to understand and control inflammation-driven diseases. The time-dependent and active process of resolution phase is orchestrated by the endogenous biosynthesis of specialized pro-resolving lipid mediators (SPMs). Inflammation and its resolution are two forces in rheumatic diseases that affect millions of people worldwide with pain as the most common experienced symptom. The pathophysiological role of SPMs in arthritis has been demonstrated in pre-clinical and clinical studies (no clinical trials yet), which highlight their active orchestration of disease control. The endogenous roles of SPMs also give rise to the opportunity of envisaging these molecules as novel candidates to improve the life quality of rhematic diseases patients. Herein, we discuss the current understanding of SPMs endogenous roles in arthritis as pro-resolutive, protective, and immunoresolvent lipids.

12/15-lipoxygenase activity promotes efficient inflammation resolution in a murine model of Lyme arthritis

“…mLA resolution is defective in C3H 12/15-LO -/mice Lipoxins and specialized proresolving mediators (SPM) are metabolites of 12/15-LO activity that are well-characterized for their ability to mediate resolution in various models of inflammation, including arthritis (27). We first characterized the expression of Alox15, the gene which encodes 12/15-LO in mice, during the time-course of mLA.…”

“…These pro-resolving lipids act through a variety of mechanisms, including inhibition of inflammatory leukocyte recruitment, induction of neutrophil apoptosis and efferocytosis, and reprogramming of macrophages towards a pro-resolving phenotype (42). Previous studies demonstrate a clear role for lipoxins and SPM in regulating inflammation in degenerative or autoimmune arthritis in humans and in mouse models of arthritis (27). Studies in rheumatoid arthritis (RA) patients demonstrated that lower levels of circulating SPM could clearly distinguish active RA patients from healthy controls, indicating a correlation between SPM expression and disease status (32,43).…”

The SIRT1-HMGB1 axis: Therapeutic potential to ameliorate inflammatory responses and tumor occurrence

“…Current treatments for arthritis have focused on disease control, and the cure still seems unreachable. Therefore, life-long therapy is required to inhibit the inflammatory process to effectively control further cartilage and bone damage ( Zaninelli et al, 2021 ). Arthritis is the leading cause of disability in the United States (US) and other populations ( Basu et al, 2018 ).…”