Interleukin-17: A new bone acting cytokine in vitro

Interleukin-17 (IL-17) is a recently cloned cytokine that is exclusively pr oduced by activated T cells, but its receptor has been found on several cel ls and tissues, Like other proinflammatory cytokines produced by activated T cells, IL-17 may affect osteoclastic resorption and thereby mediate bone destruction accompanying some inflammatory diseases. In the present study, we investigated whether osteogenic cells possess the receptor for IL-17 (IL -17R) and whether IL-17 affects osteoclastic resorption, We found that IL-1 7R mRNA is expressed both in mouse MC3T3-E1 osteoblastic cells and fetal mo use long bones, suggesting that osteogenic cells may be responsive to IL-17 , In fetal mouse long bones, IL-17 had no effect on basal and IL-1 beta-sti mulated osteoclastic bone resorption, but when given together with tumor ne crosis factor-alpha (TNF-alpha) it increased bone resorption dose dependent ly in serum-free conditions. In addition, IL-17 increased TNF-alpha-induced IL-1 alpha, IL-1 beta, and IL-6 mRNA expression in fetal mouse metatarsals and IL-1 alpha and IL-6 mRNA expression in MC3T3-E1 cells. In conclusion, IL-17R mRNA was expressed by mouse osteoblastic cells and fetal mouse long bones, and IL-17 in combination with TNF-alpha, but not IL-1 beta, increase d osteoclastic resorption in vitro. IL-17 may therefore affect bone metabol ism in pathological conditions characterized by the presence of activated T cells and TNF-alpha production such as rheumatoid arthritis and loosening of bone implants.