title: Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs.
abstract: OBJECTIVE
  Human eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin. Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines.
  
  
  RESULTS
  Eosinophils are the major source of interleukin-5 and highly express the interleukin-5Rα on their surface. Clinical trials evaluating monoclonal antibodies to interleukin-5 (mepolizumab and reslizumab) and its receptor interleukin-5Rα (benralizumab) have been or are underway in patients with eosinophilic asthma, EGPA and chronic obstructive pulmonary disease (COPD). Overall, targeting interleukin-5/interleukin-5Rα is associated with a marked decrease in blood and sputum eosinophilia, the number of exacerbations and improvement of some clinical parameters in adult patients with severe eosinophilic asthma. Pilot studies suggest that mepolizumab might be a glucocorticoid-sparing treatment in patients with EGPA. A preliminary study found that benralizumab did not reduce the exacerbations and did modify lung function in patients with eosinophilic COPD.
  
  
  CONCLUSIONS
  The review examines recent advances in the biology of eosinophils and how targeting the interleukin-5 pathway might offer benefit to some patients with severe asthma, EGPA, and COPD. Interleukin-5/interleukin-5Rα-targeted treatments offer promises to patients with eosinophilic respiratory disorders.
authors: aDepartment of Translational Medical Sciences, University of Naples Federico II, Naples bRespiratory Diseases and Allergy Clinic, DIMI-Department of Internal Medicine, Respiratory Diseases and Allergy Clinic, University of Genoa, IRCCS AOU S. Martino Genoa, Genoa cDepartment of Clinical and Experimental Medicine, Respiratory Disease and Allergology, University of Catania, Catania, Italy.
authors: Gilda
authors: G
authors: Varricchi
authors: Diego
authors: D
authors: Bagnasco
authors: Francesco
authors: F
authors: Borriello
authors: Enrico
authors: E
authors: Heffler
authors: Giorgio W
authors: GW
authors: Canonica
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D002986:Clinical Trials as Topic; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000628:therapy*; D053649:Receptors, Interleukin-5 / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D053649:Receptors, Interleukin-5