Interleukin-6 as a key player in systemic inflammation and joint destruction.
Interleukin-6 (IL-6) is a cytokine that can facilitate autoimmune phenomena, amplify acute inflammation and promote the evolution into a chronic inflammatory state. In addition, it is a major promoter of bone resorption in pathological conditions. In particular, IL-6 has a pivotal role in synovitis, bone erosions and in the systemic features of inflammation. This cytokine specifically binds to IL-6 receptor (IL-6R), forming the IL-6/IL-6R complex that binds to gp130, a membrane-bound protein, which is involved in non-ligand-binding signal transduction. Targeting IL-6R in both animal models of arthritis and in rheumatoid arthritis patients with a humanized anti IL-6R monoclonal antibody (tocilizumab) effectively controls local and systemic inflammatory manifestations and blocks cartilage and bone destruction. Given the pleiotropic function of IL-6 it can be anticipated that other inflammatory diseases and bone metabolic conditions might benefit from selective IL-6 signaling inhibition.
Fonseca
J E
JE
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. jefonseca@netcabo.pt
Santos
M J
MJ
Canhão
H
H
Choy
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000276:immunology*; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab