Cytokines disrupt the balance of the anabolic and catabolic processes within the joint leading to progressive degeneration of the joint if left unchecked.

Cytokines can be pro-inflammatory or anti-inflammatory.  It is thought that the most important pro-inflammatory cytokines in the pathogenesis of OA are IL-1β and TNF-α.  Other pro-inflammatory cytokines thought to play a role in the pathogenesis of OA include IL-6, IL-17 and IL-18.

Anti-inflammatory cytokines thought to have a role in reducing the activity or production of the pro-inflammatory cytokines include IL-4, IL-10 and IL-13.


This is one of the key cytokines involved in the pathogenesis of OA.  It is synthesised in the joint by chondrocytes, osteoblasts, synovium and mononuclear cells and is increased in the joint in OA.  In the normal joint, the balance of IL-1 and its antagonist protein, IL-1Ra, is hypothesised to be important for the maintenance of homeostasis and prevention of OA.  In OA joints, there is increased expression of the IL-1 receptor on the surface of chondrocytes and fibroblast-like synoviocytes and a reduction in the production of IL-1Ra.  IL-1Ra is produced and secreted from synoviocytes and articular chondrocytes so any damage to these cells (as in OA) will lead to a reduction in the production of this molecule and hence a reduction in its antagonistic effects against IL-1.

IL-1 stimulates the production of:

  • Prostaglandin E2 – inhibits proteoglycan synthesis, induces collagen degradation
  • Nitrous Oxide – Causes apoptosis of cells and perpetuates the expression of pro-inflammatory cytokines
  • Cytokines – pro-inflammatory cytokines
  • Chemokines – mediate recruitment and traffic inflammatory cells
  • Adhesion molecules
  • Matrix metalloproteinases (MMPs) and other enzymes involved in cartilage degradation


Over production of TNF-α in OA by activated synoviocytes and articular chondrocytes leads to further matrix degradation in articular cartilage and drives the inflammatory process further.

It causes activation of the same group of intracellular signalling pathways that are involved when IL-1β is activated so has similar effects to IL-1β. 


IL-6 production in the joint is usually in response to presence of IL-1 and TNF-α.  It is responsible for activating the immune system and and enhancing the inflammatory response.  In synergy with the other cytokines, it causes a decrease in the production of type II collagen and increases the production of MMPs and leads to resorption of subchondral bone by promoting osteoclast formation.


IL-17 is produced from stimulated CD4+ T cells and mast cells and has the following effects within the joint:

  • Inhibit synthesis of proteoglycans by chondrocytes
  • Promotes production of MMPs
  • Influences the secretion of other cytokines that negatively affect cartilage (IL-1β, TNF-α, IL-6, NO, PGE2)
  • Causes excessive development of blood vessels within the synovial membrane and hence synovial hypertrophy


Production of IL-18 in the joint is induced by IL-1β in articular chondrocytes and synovial cells

Actions of Il-18 include:

  • Increases concentration of MMPs
  • Inhibits production of type II collagen, proteoglycans and aggrecan
  • Increases the production of IL-6, inducible nitric oxide synthase (iNOS), PGE2, COX-2 and VEGF from chondrocytes and synovial cells.


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