Implication of IL-17 in Bone Loss and Structural Damage in Inflammatory Rheumatic Diseases.

Abstract

Proinflammatory cytokines play an important role in the systemic and focal bone loss associated with chronic inflammatory diseases. Targeting these cytokines with biologics and small molecules has led to a major improvement of the bone health of patients with inflammatory arthritis. Cytokines from the IL-17 family have been shown to be involved in the pathogenesis of several diseases such as spondyloarthritis, psoriatic arthritis, or psoriasis. IL-17A has been the first described and the most studied. The recent development of targeted therapies against IL-17A or its receptor and their efficacy has confirmed the importance of this cytokine in the development of inflammatory diseases. The aim of this review was to describe the effects of the IL-17 family and more particularly of IL-17A on bone and cartilage tissues. At the cellular level, IL-17A is proosteoclastogenic whereas its effects on osteoblasts depend on the stage of differentiation of these cells. In vivo, IL-17A is not required for normal bone homeostasis but plays an important role in bone loss notably in an ovariectomized mouse model of osteoporosis. Preliminary data from clinical trials showed a stabilisation of bone density in patients treated with anti-IL-17A antibodies. IL-17A plays a central role in the cartilage damage through the induction of collagenases and by decreasing the expression of their inhibitors in synergy with the other proinflammatory cytokines. The prevention of structural damage by anti-IL-17A therapies has been demonstrated in several pivotal clinical trials. Overall, blocking the IL-17A pathway seems to have a positive effect on the bone and cartilage damage observed in inflammatory arthritis. Differences and specificity of these effects compared to those already described with other biologics such as anti-TNF therapies remain to be explored.

• Authors: Benoit Le Goff, Béatrice Bouvard, Thierry Lequerre, Eric Lespessailles, Hubert Marotte, Yves-Marie Pers, Bernard Cortet
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2019 Pg. 8659302 ( 2019) ISSN: 1466-1861 [Electronic] United States
• PMID: 31485194 (Publication Type: Journal Article, Review)

Chemical References

• Cytokines
• Interleukin-17

Topics

• Animals
• Cytokines (metabolism)
• Humans
• Inflammation (immunology, metabolism)
• Interleukin-17 (therapeutic use)
• Rheumatic Diseases (metabolism)