Reslizumab

Reslizumab an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 with a dissociation constant of 81 pM. IL-5 is a proinflammatory cytokine responsible for the terminal maturation of eosinophils and increases chemotaxis, endothelial adhesion, activation and survival of eosinophils. Eosinophils are known to play a central role in the pathophysiology of many patients with asthma; upon activation, eosinophils release leukotrienes, platelet activation factor, major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and other cytokines that are cytotoxic to the bronchial epithelium and lead to airway inflammation and bronchospasm. IL-5 production is increased by upon activation of TH2 lymphocytes after antigen exposure and IL-5 stimulates the production and maturation of eosinophil precursors in the bone marrow. IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils via interacting with the IL-5 receptor expressed on the eosinophil surface. Increased production and activation of eosinophils is especially prominent in nonallergic forms of asthma.

Reslizumab is a humanized monoclonal antibody that occupies the region ERRR (glutamic acid, arginine, arginine, arginine) corresponding to amino acids 89–92 on IL-5, which is a region critical for its interaction with the IL-5 receptor on the eosinophil surface. By binding to IL-5 and disrupting its binding to the alpha chain of the IL-5 receptor complex, reslizumab inhibits the bioactivity of IL-5 and attenuates IL-5 signaling. Blocking of IL-5 signalling thereby reduces the production and survival of eosinophils and inhibits eosinophilic-driven inflammation.