Targeting interleukin-6 in inflammatory autoimmune diseases and cancers.

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine with significant functions in the regulation of the immune system. As a potent pro-inflammatory cytokine, IL-6 plays a pivotal role in host defense against pathogens and acute stress. However, increased or deregulated expression of IL-6 significantly contributes to the pathogenesis of various human diseases. Numerous preclinical and clinical studies have revealed the pathological roles of the IL-6 pathway in inflammation, autoimmunity, and cancer. Based on the rich body of studies on biological activities of IL-6 and its pathological roles, therapeutic strategies targeting the IL-6 pathway are in development for cancers, inflammatory and autoimmune diseases. Several anti-IL-6/IL-6 receptor monoclonal antibodies developed for targeted therapy have demonstrated promising results in both preclinical studies and clinical trials. Tocilizumab, an anti-IL-6 receptor antibody, is effective in the treatment of various autoimmune and inflammatory conditions notably rheumatoid arthritis. It is the only IL-6 pathway targeting agent approved by the regulatory agencies for clinical use. Siltuximab, an anti-IL-6 antibody, has been shown to have potential benefits treating various human cancers either as a single agent or in combination with other chemotherapy drugs. Several other anti-IL-6-based therapies are also under clinical development for various diseases. IL-6 antagonism has been shown to be a potential therapy for these disorders refractory to conventional drugs. New strategies, such as combination of IL-6 blockade with inhibition of other signaling pathways, may further improve IL-6-targeted immunotherapy of human diseases.

• Authors: Xin Yao, Jiaqi Huang, Haihong Zhong, Nan Shen, Raffaella Faggioni, Michael Fung, Yihong Yao
• Journal: Pharmacology & therapeutics (Pharmacol Ther) Vol. 141 Issue 2 Pg. 125-39 (Feb 2014) ISSN: 1879-016X [Electronic] England
• PMID: 24076269 (Publication Type: Journal Article, Review)
• Copyright: © 2013.

Chemical References

• Interleukin-6

Topics

• Animals
• Autoimmune Diseases (drug therapy, immunology)
• Humans
• Inflammation (drug therapy, immunology)
• Interleukin-6 (antagonists & inhibitors, immunology)
• Neoplasms (drug therapy, immunology)