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.
Keywords: AML; Autoimmune; C-reactive protein; COPD; CRC; CRP; CSC; Cancer; DLT; EAE; EGFR; IBD; IFN; IL-6; IL-6 receptor; IL-6R; Inflammation; Interleukin-6; MM; MS; MTX; Monoclonal antibody; NSCLC; RA; RCC; SJIA; SLE; SOCS; SSc; STAT; TAM; TLR; TNF; Targeted therapy; Toll-like receptor; VEGF; acute myeloid leukemia; cancer stem cells; chronic obstructive pulmonary disease; colorectal cancer; dose-limiting toxicity; epidermal growth factor receptor; experimental autoimmune encephalitis; inflammatory bowel diseases; interferon; interleukin-6; mAb; methotrexate; monoclonal antibody; multiple myeloma; multiple sclerosis; non-small cell lung cancer; renal cell carcinoma; rheumatoid arthritis; sIL-6R; sgp130; signal transducers and activators of transcription; soluble IL-6R; soluble gp130; suppressor of cytokine signaling; systemic juvenile idiopathic arthritis; systemic lupus erythematosus; systemic sclerosis; tumor necrosis factor; tumor-associated macrophage; vascular endothelial growth factor.