[Role of TNF-alpha and cytokines in the physiopathology of rheumatoid arthritis. Therapeutic perspectives]

Bull Acad Natl Med. 2003;187(5):935-54; discussion 954-5.
[Article in French]

Abstract

Rheumatoid arthritis inflammation process is characterised by the production of soluble mediators with final alteration of cartilage and bone erosions. Etiological factors of RA remain obscure, however intermediate mechanisms are better understood: proinflammatory cytokines belonging to innate as well as adeptive immunity are principal effectors. TNF alpha and IL1 beta are major components of the inflammatory process: TNF alpha is an important stimulus of cells producing inflammatory mediators (cytokines, metalloproteinases, NO, PGE2,...) and IL1 beta mediates cartilage and bone destruction (via secretion of metalloproteinases, decrease synthesis of glycosaminoglycans...). Natural inhibitors of proinflammatory cytokines are also present such as IL1-Ra for IL1 or secreted soluble receptors, sIL1-RI, sIL1-RII, sTNF-RI, sTNF-RII. The level of these inhibitors are increased but not enough to sustain an anti-inflammatory effect. Progress in animal models and in clinical practice has driven to market biological drugs targeted to inhibit TNF alpha and recently IL1 beta. Other cytokines taking place in the inflammatory cascade before TNF alpha and IL1 beta are potential future therapeutic targets such as IL18. Cytokines with anti-inflammatory effect (IL4, IL10, IL13...) can also be used for treatment of RA in association with anti-TNF alpha or anti-IL1 beta.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Experimental / etiology
  • Arthritis, Experimental / physiopathology
  • Arthritis, Experimental / therapy
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / physiopathology*
  • Disease Models, Animal
  • Drug Design
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / physiology
  • Interleukins / antagonists & inhibitors
  • Interleukins / physiology*
  • Mice
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Models, Biological
  • Receptors, Tumor Necrosis Factor / drug effects
  • Receptors, Tumor Necrosis Factor / physiology
  • Synovial Membrane / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Interleukin-1
  • Interleukins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha