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

Curr Drug Targets. 2020;21(3):213-227. doi: 10.2174/1389450120666190821161259.

Abstract

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. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) play important roles in immune responses and bone metabolism. TNF-α 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-α 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-α and IL-6 can mediate the activity of osteocytes. Furthermore, both TNF-α 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-α and IL-6 in osteoimmunology and their potential for clinical application.

Keywords: IL-6; TNF-α; osteoblast; osteoclast; osteocyte; osteoimmunology..

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Bone and Bones / immunology*
  • Bone and Bones / metabolism*
  • Humans
  • Interleukin-6 / metabolism*
  • Osteoblasts / immunology
  • Osteoblasts / metabolism
  • Osteoclasts / immunology
  • Osteoclasts / metabolism
  • Osteoporosis, Postmenopausal / immunology
  • Osteoporosis, Postmenopausal / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha