IL-12 cytokine family: new players in pathogenesis of osteoporosis

Divya Singh

doi:10.4172/2471-8416-C1-006

IL-12 cytokine family: new players in pathogenesis of osteoporosis

European Conference on Orthopedics and Osteoporosis
November 29-30 , 2018 Amsterdam , Netherlands

Divya Singh

Central Drug Research Institute, India

Posters & Accepted Abstracts: J Clin Exp Orthop

DOI: 10.4172/2471-8416-C1-006

Abstract

The interleukin 12 (IL-12) family is unique in having the only heterodimeric cytokines, including IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, IL-12 family cytokines have diverse functional effects. Both IL-12 and IL-23 are pro-inflammatory, and have been implicated in a number of autoimmune diseases. Monoclonal antibody against IL-12/IL23 (Ustekinumab) has been used for treatment of psoriatic arthritis. IL-23 deficient mice were found to be protected against development of collagen induced arthritis and moreover IL-17 producing CD4+ T cells were absent in IL-23 deficient mice. The remaining two cytokines of the family, IL-27 and IL-35 are pre-dominantly anti-inflammatory in nature. Studies have shown that deletion of IL-27 receptor in mice leads to excessive Th17 responses in experimental autoimmune encephalomyelitis (EAE). IL-27 also has been reported to provide protection against collagen-induced arthritis and rheumatoid arthritis by suppressing Th17 cells and augmenting T regulatory cell differentiation. Apart from IL-27, IL-35, serum levels are found to be quite low in conditions of rheumatoid arthritis patients. While all these cytokines have diverse functions, their role in post-menopausal osteoporosis was not looked into. Our group has determined the role of IL-27 cytokine and IL-23 neutralizing antibody in estrogen deficiency induced bone loss conditions. Our studies revealed the osteoprotective effects of IL-27 and anti-IL 23 antibody by suppression of Th17 differentiation, the major osteoclastogenic T helper subset and restoration of ovariectomy induced deterioration of trabecular bone microarchitecture. Our studies form a strong basis for using humanized IL-27 or neutralizing IL-23 antibody towards the treatment of postmenopausal osteoporosis.