The roles of small-molecule inflammatory mediators in rheumatoid arthritis

Scand J Immunol. 2021 Mar;93(3):e12982. doi: 10.1111/sji.12982. Epub 2020 Nov 1.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Although great progress has been made in the treatment of RA with antagonists of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1, the disease remains refractory in some patients. Previous studies have found that small-molecule inflammatory mediators, such as prostaglandins, leukotrienes, reactive oxygen species, nitric oxide, lipoxins and platelet-activating factor, play a significant role in the development of RA. Such compounds help to induce, maintain or reduce inflammation and could therefore be potential therapeutic targets. In this review, we describe the roles of various classes of small-molecule inflammatory mediators in RA and discuss the effects of some drugs that modulate their activity. Many drugs targeting these mediators have demonstrated good efficacy in mouse models of RA but not in patients. However, it is clear that many small-molecule inflammatory mediators play key roles in the pathogenesis of RA, and a better understanding of the underlying molecular pathways may assist in the development of targeted therapies that are efficacious in RA patients.

Keywords: rheumatoid arthritis; small-molecule inflammatory mediators; targeting therapy.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Inflammation Mediators / metabolism*
  • Interleukin-1alpha / antagonists & inhibitors
  • Interleukin-6 / antagonists & inhibitors
  • Leukotrienes / metabolism
  • Lipoxins / metabolism
  • Nitric Oxide / metabolism
  • Platelet Activating Factor / metabolism
  • Prostaglandins / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antirheumatic Agents
  • IL1A protein, human
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-1alpha
  • Interleukin-6
  • Leukotrienes
  • Lipoxins
  • Platelet Activating Factor
  • Prostaglandins
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide