IL-6: A key role in the articular damage of RA

IL-6 is a pleiotropic cytokine with a wide array of innate and adaptive immune responses.

As a mediator of chronic inflammation, IL-6 interacts with other cytokines and cells of the immune system such as T cells, B cells, activated macrophages and activated osteoclasts.

The relationship between cytokines and disease activity in RA was demonstrated in 1997.

In a study following the treatment of patients with conventional agents, it was shown that IL-6, more than C-reactive protein or TNF-alpha, was correlated with morning stiffness, joint counts, and Larsen score — a measure of articular damage.

One likely reason why IL-6 may be closely related to joint damage is through its effects on osteoclasts. Synovial fluid containing IL-6 and soluble IL-6 receptors has been shown to activate osteoclasts, which contribute to bone erosion seen in patients.

Elevated IL-6 levels have also been correlated with the number of neutrophils attracted to endothelial cells at the site of inflammation.

In addition, IL-6 activates fibroblasts and synoviocytes in the inflamed synovium.

Activation involves the secretion of matrix metalloproteinases, or MMPs, which are involved in cartilage degradation and secretion of vascular endothelial growth factor, or VEGF, which is important for the development of the vascularized pannus.

Thus, IL-6 has a major effect on joint damage in RA through its effect on joint inflammation, through its effects on neutrophil migration into the inflammatory site, through its effects on osteoclasts, which cause joint destruction, and through its effects on synoviocytes in pannus formation.