Reactome | IL6R binds IL6R inhibitors

IL6R binds IL6R inhibitors

Stable Identifier

R-HSA-9681294

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

ReviewStatus

5/5

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Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine. Its deregulation is associated with chronic inflammation, and multifactorial auto-immune disorders (Kaur et al. 2020). Tocilizumab is an anti-IL-6 receptor monoclonal antibody (mAb) with immunosuppressive action for chronic autoimmune indications such as rheumatoid arthritis (Choy et al. 2002). Satralizumab is a humanized monoclonal antibody that is approved (Heo 2020) for the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease (Rosso et al. 2020, Duchow & Bellmann-Strobl 2021). Sarilumab is a human monoclonal antibody against the interleukin-6 receptor (Xu et al. 2020) developed for the treatment of rheumatoid arthritis (Strand et al. 2020).

In a small, uncontrolled study, Xu et al. suggest tocilizumab might attenuate the "cytokine storm" seen in Covid-19 patients by resolving high levels of IL6 and other proinflammatory cytokines (Xu et al. 2020). Sarhan et al. concluded from a small study of 25 Covid-19 patients that tocilizumab administration resulted in significant therapeutic effect and improvement of all laboratory parameters (Sarhan et al. 2021). In the much larger Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, tocilizumab administered by intravenous infusion to Covid-19 patients resulted in reduced risk of death and shortened hospitalisation times (Hornby et al. 2021 preprint https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1)). China's National Health Commission has authorised tocilizumab's use to treat patients with serious COVID-19-induced lung damage (Luo et al. 2020, Zhang et al. 2020a,b). Other IL6 inhibitors need further study to assess their efficacy in Covid-19 patients (Khan et al. 2021).

Literature References

PubMed ID	Title	Journal	Year
33314148	Differential Binding of Sarilumab and Tocilizumab to IL-6Rα and Effects of Receptor Occupancy on Clinical Parameters Xu, C, Rafique, A, Potocky, T, Paccaly, A, Nolain, P, Lü, Q, Iglesias-Rodriguez, M, St John, G, Nivens, MC, Kanamaluru, V, Fairhurst, J, Ishii, T, Maldonado, R, Choy, E, Emery, P	J Clin Pharmacol	2020
32306778	Targeting IL-6 receptor in the treatment of neuromyelitis optica spectrum: a review of emerging treatment options Rosso, M, Saxena, S, Chitnis, T	Expert Rev Neurother	2020
12483717	Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial Choy, EH, Isenberg, DA, Garrood, T, Farrow, S, Ioannou, Y, Bird, H, Cheung, N, Williams, B, Hazleman, B, Price, R, Yoshizaki, K, Nishimoto, N, Kishimoto, T, Panayi, GS	Arthritis Rheum.	2002