The Two-Faced Cytokine IL-6 in Host Defense and Diseases

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.

Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion

“…Up-regulated expression of IL-6 is found in PPA models [1][39] . It is reported that IL-6 can differentiates naïve CD4 + αβT cells into Th17 cells contributed to the pathophysiologic process of immune disorders [40] . IL-12 is produced by activated macrophages.…”

Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines

“…All these findings together with basic research on the molecular properties of IL-6 family cytokines, their receptor complexes, their physiological roles, and animal-model experiments for autoimmune diseases have paved the way to developing therapeutic methods utilizing inhibitors and antibodies against cytokines. The clinical use of a humanized anti-IL-6Ra monoclonal antibody, tocilizumab, has been applied worldwide for the treatment of various inflammatory diseases, including RA (Narazaki and Kishimoto, 2018). Table 2 summarizes approved or developing inhibitors of IL-6 family cytokines and their receptors.…”

“…In relation to their clinical application, IL-6 has been well characterized as a major player in chronic inflammation, which is critical for the development of autoimmune diseases, such as rheumatoid arthritis (RA) (Hirano, 2010). Indeed, IL-6 inhibitors, including antibodies against IL-6 receptor alpha chain (IL-6Ra) or IL-6 itself, are effective treatments for various inflammatory diseases, such as RA and Castleman's disease (Boyce et al, 2018;Fajgenbaum, 2018;Narazaki and Kishimoto, 2018).…”

IL-6 During Influenza-Streptococcus pneumoniae Co-Infected Pneumonia—A Protector

“…In addition, elevated IL-6 during influenza infection has been associated with haemophagocytic syndrome resulting increased lung damage and worse outcome (21). In short, IL-6 levels vary widely depending on the type, severity and location of disease, and may result in either protection from or exacerbation of disease (11,22).…”