CoChat
Sign Up
Cited by 337Asthma and respiratory diseasesIL-33, ST2, and ILC PathwaysAllergic Rhinitis and Sensitization

Interleukin-5 in the Pathophysiology of Severe Asthma.

Open access
Pelaia, Corrado, Paoletti, Giovanni, Puggioni, Francesca, Racca, Francesca, Pelaia, Girolamo, Canonica, Giorgio Walter, Heffler, Enrico·2019·Frontiers in Physiology
DOI 10.3389/fphys.2019.01514PMC PMC6927944
Open this paper in CoChat — free accountOpen PDF

Abstract

Interleukin-5 (IL-5) exerts a central pathogenic role in differentiation, recruitment, survival, and degranulation of eosinophils. Indeed, during the last years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the powerful actions of IL-5 finalized to the induction, maintenance, and amplification of eosinophilic inflammation. Therefore, IL-5 is a suitable target for add-on biological therapies based on either IL-5 inhibition (mepolizumab, reslizumab) or blockade of its receptor (benralizumab). These modern treatments can result in being definitely beneficial for patients with severe type 2 (T2)-high eosinophilic asthma, refractory to conventional anti-inflammatory drugs such as inhaled and even systemic corticosteroids.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fphys.2019.01514

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 122 · Cited by 337

Research works printed but not linked: 119

  1. Adachi T. Alam R. (1998). The mechanism of IL-5 signal transduction. Am. J. Phys. 275, C623– C633. 10.1152/ajpcell.1998.275.3.C623 9730944 · DOI
  2. Adachi T. Choudhuri B. K. Stafford S. Sur S. Alam R. (2000). The differential role of extracellular signal-regulated kinases and p38 mitogen-activated protein kinase in eosinophil functions. J. Immunol. 165, 2198– 2204. 10.4049/jimmunol.165.4.2198, PMID: 10925307 · DOI
  3. Ahern S. Cervin A. (2019). Inflammation and endotyping in chronic rhinosinusitis—a paradigm shift. Medicina 55: E95. 10.3390/medicina55040095, PMID: 30959833 PMC6524025 · DOI
  4. Anderson W. C. III. Szefler S. J. (2019). Cost-effectiveness and comparative effectiveness of biologic therapy for asthma. Ann. Allergy Asthma Immunol. 122, 367– 372. 10.1016/j.anai.2019.01.018, PMID: 30703438 · DOI
  5. Bagnasco D. Caminati M. Ferrando M. Aloè T. Testino E. Canonica G. W. (2018a). Anti-IL-5 and IL-5Rα: efficacy and safety of new therapeutic strategies in severe uncontrolled asthma. Biomed. Res. Int. 2018: 5698212. 10.1155/2018/5698212 30519580 PMC6241368 · DOI
  6. Bagnasco D. Ferrando M. Varricchi G. Puggioni F. Passalacqua G. Canonica G. W.. (2017). Anti-interleukin 5 (IL-5) and IL-5Rα biological drugs: efficacy, safety, and future perspectives in severe eosinophilic asthma. Front. Med. 4: 135. 10.3389/fmed.2017.00135, PMID: 28913336 PMC5583162 · DOI
  7. Bagnasco D. Milanese M. Rolla G. Lombardi C. Bucca C. Heffler E. (2018b). The North-Western Italian experience with anti IL-5 therapy and comparison with regulatory trials. World Allergy Organ. J. 11: 34. 10.1186/s40413-018-0210-7 30555618 PMC6282342 · DOI
  8. Bates M. E. Green V. L. Bertics P. J. (2000). ERK1 and ERK2 activation by chemotactic factors in human eosinophils is interleukin 5-dependent and contributes to leukotriene C4 biosynthesis. J. Biol. Chem. 275, 10968– 10975. 10.1074/jbc.275.15.10968, PMID: 10753897 · DOI
  9. Bel E. H. Wenzel S. E. Thompson P. J. Prazma C. M. Keene O. N. Yancey S. W.. (2014). Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N. Engl. J. Med. 371, 1189– 1197. 10.1056/NEJMoa1403291, PMID: 25199060 · DOI
  10. Bhalla A. Mukherjee M. Nair P. (2018). Airway eosinophilopoietic and autoimmune mechanisms of eosinophilia in severe asthma. Immunol. Allergy Clin. N. Am. 38, 639– 654. 10.1016/j.iac.2018.06.003, PMID: 30342585 · DOI
  11. Bjermer L. Lemiere C. Maspero J. Weiss S. Zangrilli J. Germinaro M. (2016). Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest 150, 789– 798. 10.1016/j.chest.2016.03.032, PMID: 27056586 · DOI
  12. Bleecker E. R. FitzGerald J. M. Chanez P. Papi A. Weinstein S. F. Barker P.. (2016). Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomized, multicentre, placebo-controlled phase 3 trial. Lancet 388, 2115– 2127. 10.1016/S0140-6736(16)31324-1, PMID: 27609408 · DOI
  13. Bochner B. S. Gleich G. J. (2010). What targeting eosinophils has taught us about their role in diseases. J. Allergy Clin. Immunol. 126, 16– 25. 10.1016/j.jaci.2010.02.026 20434203 PMC2902581 · DOI
  14. Bousquet J. Chanez P. Lacoste J. Y. Barnèon G. Ghavanian N. Enander I.. (1990). Eosinophilic inflammation in asthma. N. Engl. J. Med. 323, 1033– 1039. 10.1056/NEJM199010113231505, PMID: 2215562 · DOI
  15. Broughton S. E. Dhagat U. Hercus T. R. Nero T. L. Grimbaldeston M. A. Bonder C. S.. (2012). The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling. Immunol. Rev. 250, 277– 302. 10.1111/j.1600-065X.2012.01164.x, PMID: 23046136 · DOI
  16. Brusselle G. Germinaro M. Weiss S. Zangrilli J. (2017). Reslizumab in patients with inadequately controlled late-onset asthma and elevated blood eosinophils. Pulm. Pharmacol. Ther. 43, 39– 45. 10.1016/j.pupt.2017.01.011, PMID: 28159511 · DOI
  17. Brusselle G. G. Maes T. Bracke K. R. (2013). Eosinophils in the spotlight: Eosinophilic airway inflammation in non allergic asthma. Nat. Med. 19, 977– 979. 10.1038/nm.3300, PMID: 23921745 · DOI
  18. Brussino L. Heffler E. Bucca C. Nicola S. Rolla G. (2018). Eosinophils target therapy for severe asthma: critical points. Biomed. Res. Int. 2018: 7582057. 10.1155/2018/7582057, PMID: 30498762 PMC6222236 · DOI
  19. Busse E. Bleecker R. FitzGerald J. M. Ferguson G. T. Barker P. Sproule S.. (2019). Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir. Med. 7, 46– 59. 10.1016/S2213-2600(18)30406-5, PMID: 30416083 · DOI
  20. Castro M. Mathur S. Hargreave F. Boulet L. P. Xie F. Young J.. (2011). Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am. J. Respir. Crit. Care Med. 184, 1125– 1132. 10.1164/rccm.201103-0396OC, PMID: 21852542 · DOI
  21. Castro M. Zangrilli J. Wechsler M. E. Bateman E. D. Brusselle G. G. Bardin P.. (2015). Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir. Med. 3, 355– 366. 10.1016/S2213-2600(15)00042-9, PMID: 25736990 · DOI
  22. Chipps B. E. Newbold P. Hirsch I. Trudo F. Goldman M. (2018). Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann. Allergy Asthma Immunol. 120, 504– 511. 10.1016/j.anai.2018.01.030, PMID: 29409951 · DOI
  23. Cho J. Y. Miller M. Baek K. J. Han J. W. Nayar J. Lee S. Y. (2004). Inhibition of airway remodeling in IL-5-deficient mice. J. Clin. Invest. 113, 551– 560. 10.1172/JCI19133, PMID: 14966564 PMC338264 · DOI
  24. Chupp G. L. Bradford E. S. Albers F. C. Bratton D. J. Wang-Jairaj J. Nelsen L. M.. (2017). Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase 3b trial. Lancet Respir. Med. 5, 390– 400. 10.1016/S2213-2600(17)30125-X, PMID: 28395936 · DOI
  25. Devos R. Guisez Y. Plaetinck G. Cornelis S. Tavernier J. van der Heyden J.. (1994). Covalent modification of the interleukin-5 receptor by isothiazolones leads to inhibition of the binding of interleukin-5. Eur. J. Biochem. 225, 635– 640. 10.1111/j.1432-1033.1994.00635.x, PMID: 7957178 · DOI
  26. Dorman S. C. Efthimiadis A. Babirad I. Watson R. M. Denburg J. A. Hargreave F. E.. (2004). Sputum CD34+ IL-5Rα+ cells increase after allergen: evidence for in situ eosinophilopoiesis. Am. J. Respir. Crit. Care Med. 169, 573– 577. 10.1164/rccm.200307-1004OC, PMID: 14630618 · DOI
  27. Dunican E. M. Fahy J. V. (2017). Asthma and corticosteroids: time for a more precise approach to treatment. Eur. Respir. J. 49: 1701167. 10.1183/13993003.01167-2017, PMID: 28663322 · DOI
  28. Egan R. W. Athwal D. Bodmer M. W. (1999). Effect of Sch 55700, a humanized monoclonal antibody to human interleukin-5, on eosinophilic responses and bronchial hyperreactivity. Arzneimittelforschung 49, 779– 790. 10.1055/s-0031-1300502, PMID: 10514907 · DOI
  29. Elbon C. L. Jacoby D. B. Fryer A. D. (1995). Pretreatment with an antibody to interleukin 5 prevents loss of pulmonary M2 muscarinic function in antigen challenged Guinea pigs. Am. J. Respir. Cell Mol. Biol. 12, 320– 328. 10.1165/ajrcmb.12.3.7873198, PMID: 7873198 · DOI
  30. Fainardi V. Pisi G. Chetta A. (2016). Mepolizumab in the treatment of severe eosinophilic asthma. Immunotherapy 8, 27– 34. 10.2217/imt.15.102, PMID: 26653083 · DOI
  31. Ferguson G. T. FitzGerald J. M. Bleecker E. R. Laviolette M. Bernstein D. LaForce C.. (2017). Benralizumab for patients with mild to moderate persistent asthma (BISE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Respir. Med. 5, 568– 576. 10.1016/S2213-2600(17)30190-X, PMID: 28545978 · DOI
  32. FitzGerald J. M. Bleecker E. R. Nair P. Korn S. Ohta K. Lommatzsch M.. (2016). Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 388, 2128– 2141. 10.1016/S0140-6736(16)31322-8, PMID: 27609406 · DOI
  33. Flood-Page P. Menzies-Gow A. Phipps S. Ying S. Wangoo A. Ludwig M. S.. (2003). Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J. Clin. Invest. 112, 1029– 1036. 10.1172/JCI17974, PMID: 14523040 PMC198522 · DOI
  34. Foster P. S. Hogan S. P. Ramsay A. J. Matthaei K. I. Young I. G. (1996). Interleukin 5 deficiency abolishes eosinophilia, airway hyperreactivity, and lung damage in a mouse asthma model. J. Exp. Med. 183, 195– 201. 10.1084/jem.183.1.195, PMID: 8551223 PMC2192412 · DOI
  35. Fulkerson P. C. Rothenberg M. E. (2013). Targeting eosinophils in allergy, inflammation and beyond. Nat. Rev. Drug Discov. 12, 117– 129. 10.1038/nrd3838, PMID: 23334207 PMC3822762 · DOI
  36. Galdiero M. R. Varricchi G. Seaf M. Marone G. Levi-Schaffer F. Marone G. (2017). Bidirectional mast cell-eosinophil interactions in inflammatory disorders and cancer. Front. Med. 4: 103. 10.3389/fmed.2017.00103, PMID: 28791287 PMC5523083 · DOI
  37. Ghazi A. Trikha A. Calhoun W. J. (2012). Benralizumab – a humanized mAb to IL-5Rα with enhanced antibody-dependent cell-mediated cytotoxicity – a novel approach for the treatment of asthma. Expert. Opin. Biol. Ther. 12, 113– 118. 10.1517/14712598.2012.642359 22136436 PMC3587289 · DOI
  38. Gnanakumaran G. Babu K. S. (2003). Technology evaluation: mepolizumab, GlaxoSmithKline. Curr. Opin. Mol. Ther. 5, 321– 325. PMID: 12870444
  39. Gonzalez D. Benitez M. Quirce S. (2019). Benralizumab: a new approach for the treatment of severe eosinophilic asthma. J. Investig. Allergol. Clin. Immunol. 29, 84– 93. 10.18176/jiaci.0385, PMID: 31017107 · DOI
  40. Greenfeder S. Umland S. P. Cuss F. M. Chapman R. W. Egan R. W. (2001). Th2 cytokines and asthma. The role of interleukin-5 in allergic eosinophilic disease. Respir. Res. 2, 71– 79. 10.1186/rr41, PMID: 11686868 PMC59571 · DOI
  41. Hakonarson H. Maskeri N. Carter C. Chuang S. Grunstein M. M. (1999). Autocrine interaction between IL-5 and IL-1beta mediates altered responsiveness of atopic asthmatic sensitized airway smooth muscle. J. Clin. Invest. 104, 657– 667. 10.1172/JCI7137, PMID: 10487780 PMC408541 · DOI
  42. Haldar P. (2017). Patient profiles and clinical utility of mepolizumab in severe eosinophilic asthma. Biol. Ther. Dent. 11, 81– 95. 10.2147/BTT.S93954, PMID: 28721009 PMC5498675 · DOI
  43. Haldar P. Brightling C. E. Hargadon B. Gupta S. Monteiro W. Sousa A.. (2009). Mepolizumab and exacerbations of refractory eosinophilic asthma. N. Engl. J. Med. 360, 973– 984. 10.1056/NEJMoa0808991, PMID: 19264686 PMC3992367 · DOI
  44. Hart T. K. Cook R. M. Zia-Amirhosseini P. Minthorm E. Sellers T. S. Maleeff B. E.. (2001). Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J. Allergy Clin. Immunol. 108, 250– 257. 10.1067/mai.2001.116576, PMID: 11496242 · DOI
  45. Heffler E. Malvezzi L. Boita M. Brussino L. De Virgilio A. Ferrando M.. (2018). Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps. Expert. Rev. Clin. Immunol. 14, 731– 737. 10.1080/1744666X.2018.1512407, PMID: 30107759 · DOI
  46. Heffler E. Malvezzi L. Pirola F. Zieba N. Paoletti G. Mercante G.. (2019). Treatable traits in chronic rhinosinusitis with nasal polyps. Curr. Opin. Allergy Clin. Immunol. 19, 373– 378. 10.1097/ACI.0000000000000544, PMID: 31135395 · DOI
  47. Hogan S. P. Rosenberg H. F. Moqbel R. Phipps S. Foster P. S. Lacy P.. (2008). Eosinophils: biological properties and role in health and disease. Clin. Exp. Allergy 38, 709– 750. 10.1111/j.1365-2222.2008.02958.x, PMID: 18384431 · DOI
  48. Holgate S. T. Wenzel S. Postma D. S. Weiss S. T. Renz H. Sly D. (2015). Asthma. Nat. Rev. Dis. Primers 1: 15025. 10.1038/nrdp.2015.25 27189668 PMC7096989 · DOI
  49. Houston J. C. De Navasquez S. Trounce J. R. (1953). A clinical and pathological study of fatal cases of status asthmaticus. Thorax 8, 207– 213. 10.1136/thx.8.3.207, PMID: 13102418 PMC1019266 · DOI
  50. Huber K. L. Koessler K. (1922). The pathology of bronchial asthma. Arch. Intern. Med. 30, 689– 760. 10.1001/archinte.1922.00110120002001 · DOI
  51. Ilmarinen P. Moilanen E. Kankaanranta H. (2014). Regulation of spontaneous eosinophil apoptosis – a neglected area of importance. J. Cell Death 7, 1– 9. 10.4137/JCD.S13588, PMID: 25278781 PMC4167313 · DOI
  52. Ip W. K. Wong C. K. Wang C. B. Tian Y. P. Lam C. W. (2005). Interleukin-3, -5, and granulocyte macrophage colony-stimulating factor induce adhesion and chemotaxis of human eosinophils via p38 mitogen-activated protein kinase and nuclear factor kappaB. Immunopharmacol. Immunotoxicol. 27, 371– 393. 10.1080/08923970500240925 16237950 · DOI
  53. Ishino T. Harrington A. E. Gopi H. Chaiken I. (2008). Structure-based rationale for interleukin 5 receptor antagonism. Curr. Pharm. Des. 14, 1231– 1239. 10.2174/138161208784246144, PMID: 18473871 · DOI
  54. Ishino T. Pasut G. Scibek J. Chaiken I. (2004). Kinetic interaction analysis of human interleukin 5 receptor α mutants reveals a unique binding topology and charge distribution for cytokine recognition. J. Biol. Chem. 279, 9547– 9556. 10.1074/jbc.M309327200, PMID: 14662768 · DOI
  55. Johanson K. Appelbaum E. Doyle M. Hensley P. Zhao B. Abdel-Meguid S. S.. (1995). Binding interactions of human interleukin 5 with its receptor α subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins. J. Biol. Chem. 270, 9459– 9471. 10.1074/jbc.270.16.9459, PMID: 7721873 · DOI
  56. Johansson M. V. (2017). Eosinophil activation status in separate compartments and association with asthma. Front. Med. 4: 75. 10.3389/fmed.2017.00075, PMID: 28660189 PMC5466952 · DOI
  57. Kandikattu H. K. Venkateshaiah S. U. Mishra A. (2019). Synergy of interleukin (IL)-5 and IL-18 in eosinophil mediated pathogenesis of allergic diseases. Cytokine Growth Factor Rev. 47, 83– 98. 10.1016/j.cytogfr.2019.05.003, PMID: 31126874 PMC6781864 · DOI
  58. Kay A. B. Phipps S. Robinson D. S. (2004). A role for eosinophils in airway remodelling in asthma. Trends Immunol. 25, 477– 482. 10.1016/j.it.2004.07.006, PMID: 15324740 · DOI
  59. Kips J. C. O’Connor B. J. Langley S. J. Woodcock A. Kerstjens H. A. Postma D. S.. (2003). Effects of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am. J. Respir. Crit. Care Med. 167, 1655– 1659. 10.1164/rccm.200206-525OC, PMID: 12649124 · DOI
  60. Koike M. Nakamura K. Furuya A. Iida A. Anazawa H. Takatsu K.. (2009). Establishment of humanized anti-interelukin-5 receptor α chain monoclonal antibodies having a potent neutralizing activity. Hum. Antibodies 18, 17– 27. 10.3233/HAB-2009-0198, PMID: 19478395 · DOI
  61. Kolbeck R. Kozhich A. Koike M. Peng L. Andersson C. K. Damschroder M. M.. (2010). Medi-563, a humanized anti-IL-5 receptor α mAb with enhanced antibody-dependent cell mediated cytotoxicity function. J. Allergy Clin. Immunol. 125, 1344– 1353. 10.1016/j.jaci.2010.04.004, PMID: 20513525 · DOI
  62. Kopf M. Brombacher F. Hodgkin P. D. Ramsay A. J. Milbourne E. A. Dai W. J.. (1996). IL-5 deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity 4, 15– 24. 10.1016/S1074-7613(00)80294-0, PMID: 8574848 · DOI
  63. Kouro T. Takatsu K. (2009). IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int. Immunol. 21, 1303– 1309. 10.1093/intimm/dxp102, PMID: 19819937 · DOI
  64. Kung T. T. Jones H. Adams G. K. III. Umland S. P. Kreutner W. Egan R. W. (1994). Characterization of a murine model of allergic pulmonary inflammation. Int. Arch. Allergy Immunol. 105, 83– 90. 10.1159/000236807 8086833 · DOI
  65. Kung T. T. Stelts D. M. Zurcher J. A. Adams G. K. III. Egan R. W. Kreutner W.. (1995). Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody. Am. J. Respir. Cell Mol. Biol. 13, 360– 365. 10.1165/ajrcmb.13.3.7654390, PMID: 7654390 · DOI
  66. Lambrecht B. N. Hammad H. (2015). The immunology of asthma. Nat. Immunol. 16, 45– 56. 10.1038/ni.3049, PMID: 25521684 · DOI · Paper page
  67. Lambrecht B. N. Hammad H. Fahy J. V. (2019). The cytokines of asthma. Immunity 50, 975– 991. 10.1016/j.immuni.2019.03.018, PMID: 30995510 · DOI
  68. Lilly C. M. Chapman R. W. Sehring S. J. Mauser P. J. Egan R. W. Drazen J. M. (1996). Effects of interleukin 5-induced pulmonary eosinophilia on airway reactivity in the Guinea pig. Am. J. Phys. 270, L368– L375. 10.1152/ajplung.1996.270.3.L368, PMID: 8638729 · DOI
  69. Makinde T. Murphy R. F. Agrawall D. K. (2007). The regulatory role of TGF-beta in airway remodeling in asthma. Immunol. Cell Biol. 85, 348– 356. 10.1038/sj.icb.7100044, PMID: 17325694 · DOI
  70. Marichal T. Mesnil C. Bureau F. (2017). Homeostatic eosinophils: characteristics and functions. Front. Med. 4: 101. 10.3389/fmed.2017.00101, PMID: 28744457 PMC5504169 · DOI
  71. Mauser P. J. Pitman A. M. Fernandez X. Foran S. K. Adams G. K. III. Kreutner W.. (1995). Effects of an antibody to interleukin-5 in a monkey model of asthma. Am. J. Respir. Crit. Care Med. 152, 467– 472. 10.1164/ajrccm.152.2.7633694, PMID: 7633694 · DOI
  72. Mauser P. J. Pitman A. Witt A. Fernandez X. Zurcher J. Kung T.. (1993). Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a Guinea pig model of asthma. Am. Rev. Respir. Dis. 148, 1623– 1628. 10.1164/ajrccm/148.6_Pt_1.1623, PMID: 7504892 · DOI
  73. McGregor M. C. Krings J. G. Nair P. Castro M. (2019). Role of biologics in asthma. Am. J. Respir. Crit. Care Med. 199, 433– 445. 10.1164/rccm.201810-1944CI, PMID: 30525902 PMC6835092 · DOI
  74. Minai-Fleminger Y. Elishmereni M. Vita F. Soranzo M. R. Mankuta D. Zabucchi G.. (2010). Ultrastructural evidence for human mast cell-eosinophil interactions in vitro. Cell Tissue Res. 341, 405– 415. 10.1007/s00441-010-1010-8, PMID: 20686785 · DOI
  75. Molfino N. A. Gossage D. Kolbeck R. Parker J. M. Geba G. P. (2012). Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin. Exp. Allergy 42, 712– 737. 10.1111/j.1365-2222.2011.03854.x, PMID: 22092535 · DOI
  76. Murphy J. M. Young I. G. (2006). IL-3, IL-5, and GM-CSF signaling crystal structure of the human beta-common receptor. Vitam. Horm. 74, 1– 30. 10.1016/S0083-6729(06)74001-8 17027509 · DOI
  77. Nair P. Pizzichini M. M. Kjarsgaard M. Inman M. D. Efthimiadis A. Pizzichini E.. (2009). Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N. Engl. J. Med. 360, 985– 993. 10.1056/NEJMoa0805435, PMID: 19264687 · DOI
  78. Nair P. Wenzel S. Rabe K. F. Bourdin A. Lugogo N. L. Kuna P.. (2017). Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N. Engl. J. Med. 376, 2448– 2458. 10.1056/NEJMoa1703501, PMID: 28530840 · DOI
  79. Ohnishi T. Sur S. Collins D. S. Fish J. E. Gleich G. J. Peters S. P. (1993). Eosinophil survival activity identified as interleukin-5 is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge. J. Allergy Clin. Immunol. 92, 607– 615. 10.1016/0091-6749(93)90085-T, PMID: 8409120 · DOI
  80. Ortega H. G. Liu M. C. Pavord I. D. Brusselle G. G. FitzGerald J. M. Chetta A.. (2014). Mepolizumab treatment in patients with severe eosinophilic asthma. N. Engl. J. Med. 371, 1198– 1207. 10.1056/NEJMoa1403290, PMID: 25199059 · DOI
  81. Park S. W. Kim D. Chang H. S. Park S. J. Lee Y. M. Park J. S.. (2003). Association of interleukin-5 and eotaxin with acute exacerbation of asthma. Int. Arch. Allergy Immunol. 131, 283– 290. 10.1159/000072140, PMID: 12915771 · DOI
  82. Pavord I. D. Korn S. Howarth P. Bleecker E. R. Buhl R. Keene O. N.. (2012). Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 380, 651– 659. 10.1016/S0140-6736(12)60988-X, PMID: 22901886 · DOI
  83. Pazdrak K. Olszewska-Pazdrak B. Stafford S. Garofalo R. P. Alam R. (1998). Lyn, Jak2, and Raf-1 kinases are critical for the antiapoptotic effect of interleukin-5, whereas only Raf-1 kinase is essential for eosinophil activation and degranulation. J. Exp. Med. 188, 421– 429. 10.1084/jem.188.3.421, PMID: 9687520 PMC2212466 · DOI
  84. Pazdrak K. Stafford S. Alam R. (1995). The activation of the Jak-STAT 1 signalling pathway by IL-5 in eosinophils. J. Immunol. 155, 397– 402. PMID: 7602114
  85. Pelaia C. Busceti M. T. Solinas S. Terracciano R. Pelaia G. (2018a). Real-life evaluation of the clinical, functional, and hematological effects of mepolizumab in patients with severe eosinophilic asthma: results of a single-centre observational study. Pulm. Pharmacol. Ther. 53, 1– 5. 10.1016/j.pupt.2018.09.006 30217438 · DOI
  86. Pelaia C. Busceti M. T. Vatrella A. Rago G. F. Crimi C. Terracciano R.. (2019). Real-life rapidity of benralizumab effects in patients with severe allergic asthma: assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose. Pulm. Pharmacol. Ther. 58101830. 10.1016/j.pupt.2019.101830, PMID: [Epub ahead of print]. 31344472 · DOI
  87. Pelaia C. Calabrese C. Vatrella A. Busceti M. T. Garofalo E. Lombardo N. (2018c). Benralizumab: from the basic mechanism of action to the potential use in the biological therapy of severe eosinophilic asthma. Biomed. Res. Int. 2018: 4839230. 10.1155/2018/4839230 29862274 PMC5971345 · DOI
  88. Pelaia G. Cuda G. Vatrella A. Gallelli L. Caraglia M. Marra M.. (2005). Mitogen-activated protein kinases and asthma. J. Cell. Physiol. 202, 642– 653. 10.1002/jcp.20169, PMID: 15316926 · DOI
  89. Pelaia C. Vatrella A. Bruni A. Terracciano R. Pelaia G. (2018b). Benralizumab in the treatment of severe asthma: design, development and potential place in therapy. Drug Des. Devel. Ther. 12, 619– 628. 10.2147/DDDT.S155307 PMC5868576 29606855 · DOI
  90. Pelaia G. Vatrella A. Busceti M. T. Gallelli L. Calabrese C. Terracciano R. (2015). Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediat. Inflamm. 2015: 879783. 10.1155/2015/879783 PMC4386709 25878402 · DOI
  91. Pelaia G. Vatrella A. Busceti M. T. Gallelli L. Preianò M. Lombardo N. (2016). Role of biologics in severe eosinophilic asthma: focus on reslizumab. Ther. Clin. Risk Manag. 12, 1075– 1082. 10.2147/TCRM.S111862 27445482 PMC4936812 · DOI
  92. Pelaia C. Vatrella A. Busceti M. T. Gallelli L. Terracciano R. Savino R. (2017). Severe eosinophilic asthma: from the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des. Devel. Ther. 11, 3137– 3144. 10.2147/DDDT.S150656 PMC5669784 29133975 · DOI
  93. Rossjohn J. McKinstry W. J. Woodcock J. M. McClure B. J. Hercus T. R. Parker M. W.. (2000). Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist. Blood 95, 2491– 2498. 10.1182/blood.V95.8.2491, PMID: 10753826 · DOI
  94. Sakuishi K. Oki S. Araki M. Porcelli S. A. Miyake S. Yamamura T. (2007). Invariant NKT cells biased for IL-5 production act as crucial regulators of inflammation. J. Immunol. 179, 3452– 3462. 10.4049/jimmunol.179.6.3452, PMID: 17785779 · DOI
  95. Sano M. Leff A. R. Myou S. Boetticher E. Meliton A. Y. Learoyd J.. (2005). Regulation of interleukin-5-induced beta2-integrin adhesion of human eosinophils by phosphoinositide 3-kinase. Am. J. Respir. Cell Mol. Biol. 33, 65– 70. 10.1165/rcmb.2005-0076OC, PMID: 15802551 PMC2715304 · DOI
  96. Schleich F. Brusselle G. Louis R. Vandenplas O. Michils A. Pilette C.. (2014). Heterogeneity of phenotypes in severe asthma. The Belgian severe asthma registry (BSAR). Respir. Med. 108, 1723– 1732. 10.1016/j.rmed.2014.10.007, PMID: 25456708 · DOI
  97. Schwartz C. Willebrand R. Huber S. Rupec R. A. Wu D. Locksley R.. (2015). Eosinophil-specific deletion of IκBα in mice reveals a critical role of NFκB-induced Bcl-xL for inhibition of apoptosis. Blood 125, 3896– 3904. 10.1182/blood-2014-10-607788, PMID: 25862560 PMC4473117 · DOI
  98. Shakoory B. Fitzgerald S. M. Lee S. A. Chi D. S. Krishnaswamy G. (2004). The role of human mast cell-derived cytokines in eosinophil biology. J. Interf. Cytokine Res. 24, 271– 281. 10.1089/107999004323065057, PMID: 15153310 · DOI
  99. Shields R. L. Lai J. Keck R. O’Connell L. Y. Hong K. Meng Y. G.. (2002). Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to Fcgamma RIII and antibody-dependent cellular toxicity. J. Biol. Chem. 277, 26733– 26740. 10.1074/jbc.M202069200, PMID: 11986321 · DOI · Paper page
  100. Siddiqui S. Denlinger L. C. Fowler S. J. Akuthota P. Shaw D. E. Heaney L. G.. (2019). Unmet needs in severe asthma subtyping and precision medicine trials. Bridging clinical and patient perspectives. Am. J. Respir. Crit. Care Med. 199, 823– 829. 10.1164/rccm.201809-1817PP, PMID: 30726120 PMC6835084 · DOI
  101. Smith S. G. Chen R. Kjarsgaard M. Huang C. Oliveria J. P. O’Byrne P. M.. (2016). Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J. Allergy Clin. Immunol. 137, 75– 86. 10.1016/j.jaci.2015.05.037, PMID: 26194544 · DOI
  102. Stirling R. G. van Rensen E. I. Barnes P. J. Chung K. F. (2001). Interleukin-5 induces CD34+ eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma. Am. J. Respir. Crit. Care Med. 164, 1403– 1409. 10.1164/ajrccm.164.8.2010002, PMID: 11704586 · DOI
  103. Stout B. A. Bates M. E. Liu L. Y. Farrington N. N. Bertics P. J. (2004). IL-5 and granulocyte-macrophage colony-stimulating factor acyivate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils. J. Immunol. 173, 6409– 6417. 10.4049/jimmunol.173.10.6409, PMID: 15528381 · DOI
  104. Takatsu K. Nakajima H. (2008). IL-5 and eosinophilia. Curr. Opin. Immunol. 20, 288– 294. 10.1016/j.coi.2008.04.001, PMID: 18511250 · DOI
  105. Tanaka H. Komai M. Nagao K. (2004). Role of IL-5 and eosinophils in allergen-induced airway remodeling in mice. Am. J. Respir. Cell Mol. Biol. 31, 62– 68. 10.1165/rcmb.2003-0305OC, PMID: 14975941 · DOI
  106. Thompson-Souza G. A. Gropillo I. Neves J. S. (2017). Cysteynil leukotrienes in eosinophil biology: functional roles and therapeutic perspectives in eosinophilic disorders. Front. Med. 4: 106. 10.3389/fmed.2017.00106, PMID: 28770202 PMC5515036 · DOI
  107. Uings I. McKinnon M. (2002). Development of IL-5 receptor antagonists. Curr. Pharm. Des. 8, 1837– 1844. 10.2174/1381612023393800 12171535 · DOI
  108. Varricchi G. Bagnasco D. Borriello F. Heffler E. Canonica G. W. (2016). Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Curr. Opin. Allergy Clin. Immunol. 16, 186– 200. 10.1097/ACI.0000000000000251, PMID: 26859368 PMC4768650 · DOI
  109. Varricchi G. Bagnasco D. Ferrando M. Puggioni F. Passalacqua G. Canonica G. W. (2017a). Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience. Ther. Adv. Respir. Dis. 11, 40– 45. 10.1177/1753465816673303 27856823 PMC5941977 · DOI
  110. Varricchi G. Canonica G. W. (2016). The role of interleukin-5 in asthma. Expert. Rev. Clin. Immunol. 12, 903– 905. 10.1080/1744666X.2016.1208564, PMID: 27450970 · DOI
  111. Varricchi G. Senna G. Loffredo S. Bagnasco D. Ferrando M. Canonica G. W. (2017b). Reslizumab and eosinophilic asthma: one step closer to precision medicine? Front. Immunol. 8: 242. 10.3389/fimmu.2017.00242 28344579 PMC5344894 · DOI
  112. Walker J. A. Barlow J. L. McKenzie A. M. (2013). Innate lymphoid cells: how did we miss them? Nat. Rev. Immunol. 13, 75– 87. 10.1038/nri3349, PMID: 23292121 · DOI
  113. Walsh G. M. (2015). Mepolizumab-based therapy in asthma: an update. Curr. Opin. Allergy Clin. Immunol. 15, 392– 396. 10.1097/ACI.0000000000000183, PMID: 26110690 · DOI
  114. Wood L. J. Sehmi R. Dorman S. Hamid Q. Tulic M. K. Watson R. M.. (2002). Allergen-induced increases in bone marrow T lymphocytes and interleukin-5 expression in subjects with asthma. Am. J. Respir. Crit. Care Med. 166, 883– 889. 10.1164/rccm.2108015, PMID: 12231502 · DOI
  115. Woodruff P. G. Modrek B. Choy D. F. Jia G. Abbas A. R. Ellwanger A.. (2009). T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am. J. Respir. Crit. Care Med. 180, 388– 395. 10.1164/rccm.200903-0392OC, PMID: 19483109 PMC2742757 · DOI
  116. Xu J. Jiang F. Nayeri F. Zetterstrom O. (2007). Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin. Respir. Med. 101, 1447– 1454. 10.1016/j.rmed.2007.01.026, PMID: 17379492 · DOI
  117. Yanagibashi T. Satoh T. M. Nagai Y. Koike M. Takatsu K. (2017). Allergic diseases: from bench to clinic – contribution of the discovery of IL-5. Cytokine 98, 59– 70. 10.1016/j.cyto.2016.11.011 28863833 · DOI
  118. Zhang J. Kuvelkar R. Murgolo N. J. Taremi S. S. Chou C. C. Wang P.. (1999). Mapping and characterization of the epitope(s) of Sch 55700, a humanized mAb, that inhibits human IL-5. Int. Immunol. 11, 1935– 1944. 10.1093/intimm/11.12.1935, PMID: 10590259 · DOI
  119. Zhang X. Moilanen C. E. Kankaanranta H. (2000). Enhancement of human eosinophil apoptosis by fluticasone propionate, budesonide, and beclomethasone. Eur. J. Pharmacol. 406, 325– 332. 10.1016/S0014-2999(00)00690-7, PMID: 11040338 · DOI

Authors
Pelaia, C., Paoletti, G., Puggioni, F., Racca, F., Pelaia, G., Canonica, G. W., & Heffler, E.
Affiliations
  • Magna Graecia University (IT)
  • Humanitas University (IT)
Corresponding author
Heffler, Enrico
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2019-12-17
Volume
10
Pages
1514-1514
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2019.01514
PMC
PMC6927944
OpenAlex
W2995236062
Cited by
337
References
122
Citations by year
2026: 44 · 2025: 73 · 2024: 66 · 2023: 52 · 2022: 40 · 2021: 37 · 2020: 23 · 2019: 1 · 2018: 1
FWCI
2.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
Keywords
IL-5, severe asthma, eosinophils, eosinophilic inflammation, type 2 inflammation, mepolizumab, reslizumab, benralizumab, anti-IL-5 therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review