Clinical Information

Interleukin 6 (IL-6) has important roles in both innate and adaptive immunity.(1) IL-6 can be produced by a variety of different cell types, including macrophages, endothelial cells, and T cells. This production can be initiated in response to microbial invasion or other cytokines, such as tumor necrosis factor. As part of the innate immune system, IL-6 acts on hepatocytes to induce expression of C-reactive protein (CRP), fibrinogen, and serum amyloid A, also known as the acute phase response. Within the adaptive immune response, IL-6 plays a key role in activating antibody-producing B cells to proliferate, leading to an enhanced antibody response.

Concentrations of IL-6 are elevated in patients with infection, sepsis, and septicemia. During inflammatory conditions, the concentration of IL-6 can increase severalfold, highlighting its clinical relevance as a major alarm signal in response to infections (sepsis/septicemia), inflammation, autoimmunity, and cancer, including Castleman disease. In addition, IL-6 concentrations appear to correlate with the severity of sepsis, as defined by clinical and laboratory parameters.(2) Elevations in IL-6 also appear to be associated with more localized infections, such as prosthetic joint infections (PJI).(3) A recent meta-analysis demonstrated that IL-6 had improved diagnostic accuracy for PJI compared to CRP, erythrocyte sedimentation rate, and white blood cell counts. IL-6 is also elevated in numerous chronic inflammatory disorders, including rheumatoid arthritis (RA), systemic lupus erythematosus, ankylosing spondylitis, and inflammatory bowel disease.(4)

There is evidence that IL-6 is involved in the pathogenesis of certain chronic inflammatory disorders. Tocilizumab, an antibody that blocks IL-6 function by binding to the IL-6 receptor, has been approved for the treatment of RA. In a randomized trial, 50% to 60% of patients receiving tocilizumab and methotrexate showed improvement in clinical signs and symptoms of RA, compared to only 25% of patients receiving methotrexate alone.(5) Siltuximab, a monoclonal antibody against IL-6, is also sometimes used to treat Castleman disease. However, the presence of Siltuximab may interfere with some IL-6 assays, leading to the proposed use of CRP as a surrogate marker to monitor Siltuximab efficacy.(6-8)

IL-6 has also been shown to be elevated in COVID-19 patients. There is some indication that patients with more severe disease may develop elevated circulating IL-6. The significance of this finding is still being elucidated, including whether monitoring of circulating IL-6 levels can help with patient management, prognosis, or response to treatment.(9,10)