TNF-α and IL-6: The Link between Immune and Bone System

Osteoimmunology is a new subject which focuses on the communication between the immune and the skeletal systems. Both the immune system and bone communicate with each other. Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play important roles in immune responses and bone metabolism. TNF-alpha and IL-6 enhance macrophage activation and antigen presentation, as well as regulating immunity through different mechanisms. A variety of groups have reported that TNF-alpha suppresses osteoblasts activity at some stages of differentiation and stimulates osteoclast proliferation and differentiation. In contrast, IL-6 mediates the actions of osteoblasts and osteoclasts through sophisticated mechanisms, which reflect dual effects. Both TNF-alpha and IL-6 can mediate the activity of osteocytes. Furthermore, both TNF-alpha and IL-6 are important pathogenic factors related to immune-mediated bone diseases including rheumatoid arthritis and postmenopausal osteoporosis. This review will discuss the contradictory findings concerning TNF-alpha and IL-6 in osteoimmunology and their potential for clinical application.