Abstract
Interleukein-6 (IL-6), is produced locally from infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions. However, excessive or sustained production of IL-6 is involved in various diseases. In diseases, the IL-6 inhibitory strategy begins with the development of the anti-IL-6 receptor antibody, tocilizumab (TCZ). This antibody has shown remarkable effects on Castleman disease, rheumatoid arthritis and juvenile idiopathic arthritis. In 2017, TCZ was proven to work effectively against giant cell arteritis, Takayasu arteritis and cytokine releasing syndrome, initiating a new era for the treatment of these diseases. In this study, the defensive functions of IL-6 and various pathological conditions are compared. Further, the diseases of which TCZ has been approved for treatment are summarized, the updated results of increasing off-label use of TCZ for various diseases are reviewed and the conditions for which IL-6 inhibition might have a beneficial role are discussed. Given the involvement of IL-6 in many pathologies, the diseases that can be improved by IL-6 inhibition will expand. However, the important role of IL-6 in host defense should always be kept in mind in clinical practice.
Highlights
Interleukein-6 (IL-6) is an essential cytokine that transmits defense signals from a pathogen invasion or tissue damage site to stimulate acute phase reactions, immune responses, hematopoiesis and various internal organs to prepare for host defense [1]
IL-6 inhibitory therapy is expected to be used for other inflammatory diseases given its strong inflammation suppressing effect and safety profile
Various biologics that interact with the extracellular domain of the IL-6 receptor complex components and low molecular weight compounds that interact with intracellular signaling molecules are being developed one after the other [200]
Summary
Interleukein-6 (IL-6) is an essential cytokine that transmits defense signals from a pathogen invasion or tissue damage site to stimulate acute phase reactions, immune responses, hematopoiesis and various internal organs to prepare for host defense [1]. Excessive and sustained production of IL-6 is associated with various inflammatory diseases [2,3,4,5]. Values of more than 1000 pg/mL can occur during septic shock or a cytokine storm and in severe cases, a level measured in μg/mL can be reached, in which excessive defense signaling can threaten survival [6]. In 2017, TCZ was approved for treatment of giant cell arteritis, Takayasu arteritis and an artificial T cell therapy-induced cytokine releasing syndrome in leukemia/lymphoma. The successful results achieved with TCZ have changed the therapeutic strategies for these conditions and it is expected that IL-6-targeting therapy could be used in many refractory diseases; clinical trials are underway
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