. 2020 Apr 23;16(6):335–345. doi: 10.1038/s41584-020-0419-z

Table 1.

Evidence for the effects of IL-6 inhibition on diseases

Disease	Cell-based assays	Animal models	Biomarkers	Clinical trials	Drugs indicated
Multiple myeloma	IL-6 promotes myeloma cell proliferation¹³	In the KPMM2 xenograft model, growth is IL-6 dependent¹⁷⁶	Serum concentrations of IL-6 correlate with disease severity in plasma cell leukaemia¹⁷⁷	No improvement in clinical outcomes^14,16	None
Crohn’s disease	IL-6 activates mucosal T cells¹⁷⁸	IL-6R blockade promotes T cell apoptosis, which contributes to chronic intestinal inflammation in the CD4 adoptive transfer colitis model¹⁷⁸	Serum concentrations of sIL-6R are increased in active disease²⁴; concentrations of IL-6 and sIL-6R are increased in colonic organ cultures using specimens from patients with active disease¹⁷⁹	Tocilizumab had a clinical effect in a pilot study²⁵	None
Castleman disease	IL-6 is produced by affected germinal centres¹⁷	Il6 transgenic mice develop clinical features of Castleman disease¹⁹	Increased serum concentrations of IL-6 in active disease¹⁷	Tocilizumab and siltuximab showed efficacy in clinical studies^22,23	Tocilizumab, siltuximab
RA	IL-6 is involved in osteoporosis, cartilage destruction and synovial inflammation associated with RA^27–29	IL-6 inhibition prevented development of arthritis in collagen-induced arthritis^31,32 and antibody-induced arthritis³³	Serum concentrations of IL-6 are elevated in active RA	IL-6 pathway inhibition is effective in many clinical trials^{36–52,54–57,62}	Tocilizumab, sarilumab
Systemic JIA	Increased production of IL-6 by PBMCs¹⁸⁰	Il6 transgenic mice develop a skeletal phenotype resembling abnormalities observed in children with chronic inflammatory diseases⁸⁴	Serum concentrations of IL-6 are increased in patients with JIA and correlate with disease activity^81,181	Tocilizumab improved disease activity and reversed growth retardation^{86–91,93,95,182}	Tocilizumab
Adult-onset Still’s disease	NA	NA	Serum concentrations of IL-6 are increased¹⁸³	Tocilizumab showed some clinical benefit and steroid-sparing effects⁹⁴	Tocilizumab
Ankylosing spondylitis	NA	NA	Serum concentrations of IL-6 are increased and correlate with disease activity¹⁰²	Tocilizumab and sarilumab failed to show therapeutic benefit in randomized controlled trials^103,104	None
Psoriatic arthritis	NA	NA	Serum and synovial fluid concentrations of IL-6 are increased^106,107	Clazakizumab improved arthritis, enthesitis and dactylitis but not skin disease¹⁰⁸	None
Systemic lupus erythematosus	Increased production of IL-6 by B cells¹⁸⁴	IL-6 implicated in autoimmune disease pathogenesis in NZB/W F1 mice¹⁰⁹	IL-6 concentrations increased in cerebrospinal fluid¹¹⁰	IL-6 pathway inhibition affected autoantibody-producing cells, but no clinically meaningful benefit demonstrated^112,113	None
Systemic sclerosis	Increased production of IL-6 by PBMCs¹⁸⁵	IL-6 blockade improved disease in the bleomycin mouse model¹¹⁶	Production of IL-6 increased in dermal fibroblasts and serum concentrations of IL-6 increased^117,118	Tocilizumab had a potentially clinically important effect on the preservation of lung function^120,121	None
Giant cell arteritis	NA	NA	Serum concentrations of IL-6 increased in active disease¹²⁴	Tocilizumab was superior to placebo with regard to sustained glucocorticoid-free remission^126,127	Tocilizumab
Takayasu arteritis	NA	NA	Serum concentrations of IL-6 increased in active disease¹²⁵	Tocilizumab had some effect on time to relapse, but the primary end point was not met¹²⁹	Tocilizumab
CRS	NA	NA	Serum concentrations of IL-6 increased¹³⁶	Tocilizumab was used to successfully treat CRS occurring in trials of CAR T cell therapy^136,137	Tocilizumab

CAR, chimeric antigen receptor; CRS, cytokine release syndrome; JIA, juvenile idiopathic arthritis; NA, not available; PBMC, peripheral blood mononuclear cell; RA, rheumatoid arthritis; sIL-6R, soluble IL-6 receptor.