Targeting IL-6 in the treatment of inflammatory and autoimmune diseases.
BACKGROUND
IL-6, a glycoprotein composed of 212 amino acids in human, has a wide range of biological activity, including regulation of immune response, support of hematopoiesis, generation of acute-phase reactions and induction of inflammation and oncogenesis. Several approaches including inhibition of IL-6 production, blockage of IL-6 binding to IL-6 receptor, blockage of IL-6/IL-6R complex binding to gp 130 and blockage of the intracytoplasmic signal through gp 130 can be used to block IL-6 functions.


OBJECTIVE
To summarize pre-clinical development and efficacy and safety of anti-IL-6 therapies in the treatment of inflammatory and autoimmune diseases.


METHODS
Journal articles found within a PubMed search and data presented in abstract form from international conferences up to May 2009 are described in this review.


CONCLUSIONS
Tocilizumab, which blocks IL-6 binding to IL-6 receptor, used as monotherapy or in combination with methotrexate for RA therapy leads to significant clinical response and amelioration of joint damage, which is superior to methotrexate. Some adverse events such as liver function disorders, hyperlipidemia, neutropenia, diarrhea and infection are observed in clinical trials. IL-6 blockers targeting directly IL-6 rather than the IL-6 receptor and fully human monoclonal antibody targeting the IL-6 receptor are currently under development. Overall, targeting IL-6 has provided a promising approach in the management of some inflammatory and autoimmune diseases.
Ding
Changhai
C
Monash University, Central and Eastern Clinical School, Department of Epidemiology and Preventive Medicine, Commercial Road, Melbourne 3004, Australia. changhai.ding@utas.edu.au
Cicuttini
Flavia
F
Li
Jun
J
Jones
Graeme
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000503:physiopathology; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab