Metabolic Checkpoints in Rheumatoid Arthritis

Abstract

Several studies have highlighted the interplay between metabolism, immunity and inflammation. Both tissue resident and infiltrating immune cells play a major role in the inflammatory process of rheumatoid arthritis (RA) via the production of cytokines, adipocytokines and metabolic intermediates. These functions are metabolically demanding and require the most efficient use of bioenergetic pathways. The synovial membrane is the primary site of inflammation in RA and exhibits distinctive histological patterns characterized by different metabolism, prognosis and response to treatment. In the RA synovium, the high energy demand by stromal and infiltrating immune cells, causes the accumulation of metabolites, and adipo-cytokines, which carry out signaling functions, as well as activating transcription factors which act as metabolic sensors. These events drive immune and joint-resident cells to acquire pro-inflammatory effector functions which in turn perpetuate chronic inflammation. Whether metabolic changes are a consequence of the disease or one of the causes of RA pathogenesis is still under investigation. This review covers our current knowledge of cell metabolism in RA. Understanding the intricate interactions between metabolic pathways and the inflammatory and immune responses will provide more awareness of the mechanisms underlying RA pathogenesis and will identify novel therapeutic options to treat this disease.

<p>Inflammation, Bone Healing and Osteonecrosis: From Bedside to Bench</p>

“…Chronic inflammation is also a state of heightened energy demands, in which organelles such as the mitochondria, endoplasmic reticulum, and other important components of the cell become exhausted, inefficient, dysfunctional, and dysregulated. [13][14][15] If chronic inflammation persists, the resilience and survival of the organism are at risk.…”

The Lipid Paradox as a Metabolic Checkpoint and Its Therapeutic Significance in Ameliorating the Associated Cardiovascular Risks in Rheumatoid Arthritis Patients

“…RA is an inflammatory disorder of the immune system, characterized by the production of self-antibodies such as ACPA, RF and anti-carbamylated protein antibodies (anti-CarP). [ 34 ]. This is accompanied by chronic inflammation of the synovial tissue and hyperplasia, damage to the bone and cartilage as well as systemic complexities, significantly related to the lungs, brain or CV system, which pose a fundamental threat to the socioeconomic balance and unmet needs [ 34 , 35 ].…”

“…[ 34 ]. This is accompanied by chronic inflammation of the synovial tissue and hyperplasia, damage to the bone and cartilage as well as systemic complexities, significantly related to the lungs, brain or CV system, which pose a fundamental threat to the socioeconomic balance and unmet needs [ 34 , 35 ]. RA is associated with progressive therapeutic advancement with conventional treatment therapies and disease modifying anti-rheumatic drugs (DMARDS); however, these agents have been able to provide optimum response in only 60% of the RA patients [ 36 ].…”

“…The immune system intolerance is marked as a primary event in RA pathogenesis, which is followed by inflammation of the joint [ 5 , 38 ], which is most likely to take place at the extracellular site [ 39 ]. The events (such as infiltration of leukocytes, production of new vasculature and elevated expression levels of chemokines and adhesion molecules) result in enhanced migration of leukocytes to the site of inflammation [ 34 ]. Furthermore, improper formation of lymphatic vessels restricts cell retreat, along with activation of fibroblasts, resulting in inflammation of the synovial tissue [ 40 ].…”

Editorial: Cross Talk Between the Immune System and Metabolism

“…For example, the activation of type 1 immunity was identified in obesity-associated metabolic dysfunction (1). Metabolism has been shown to play a critical role in RA, a chronic autoimmune disease with involvement of a series of pro-inflammatory and immune-regulatory cytokines and mediators (2,3). Innate immunity is also of key importance in the pathogenesis of gout (4).…”