Biological Treatments: New Weapons in the Management of Monogenic Autoinflammatory Disorders
Figure 1
Mechanisms of IL-1, IL-6, and TNF-α targeted therapies. Binding of IL-6 to the IL-6 receptor complex, involving IL-6 receptor (IL-6R) and glycoprotein 130 (gp130), leads to activation of IL-6 signal transduction. Tocilizumab, a recombinant humanized anti-IL-6 receptor antibody, inhibits the binding of IL-6 to IL-6R or soluble IL-6R (sIL-6R), thus blocking IL-6 inflammatory response. Binding of IL-1β to the IL-1 receptor type I (IL-1RI) promotes a receptor complex formation with the IL-1 receptor accessory protein (IL-1RAcP), that results in signal transduction activation. IL-1-targeted therapy includes anakinra (IL-1R receptor antagonist), canakinumab (anti-IL-1β IgG1 mAb), and rilonacept (soluble IL-1 receptor that binds IL-1β, IL-1α, and IL1RA). Adalimumab, infliximab, and etanercept are anti-TNF blockers. Adalimumab is a fully human monoclonal anti-TNF antibody. Infliximab is a mouse/human chimeric monoclonal anti-TNF antibody. Etanercept is a dimeric fusion protein of TNFR2 (p75) linked with the Fc region of human IgG1.
