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Review
. 2022 Nov;12(11):1413-1423.
doi: 10.1002/alr.22994. Epub 2022 Apr 11.

The roles of eosinophils and interleukin-5 in the pathophysiology of chronic rhinosinusitis with nasal polyps

Philippe Gevaert  1 , Joseph K Han  2 , Steven G Smith  3 , Ana R Sousa  4 , Peter H Howarth  5   6 , Steven W Yancey  3 , Robert Chan  4 , Claus Bachert  1   7
Affiliations
Review

The roles of eosinophils and interleukin-5 in the pathophysiology of chronic rhinosinusitis with nasal polyps

Philippe Gevaert et al. Int Forum Allergy Rhinol. 2022 Nov.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with eosinophilic tissue infiltration linked to type 2 inflammation and characterized by elevated levels of interleukin (IL)-5 and other type 2 inflammatory mediators. Although distinct and overlapping contributions of eosinophils and IL-5 to CRSwNP pathology are still being explored, they are both known to play an important role in NP inflammation. Eosinophils secrete numerous type 2 inflammatory mediators including granule proteins, enzymes, cytokines, chemokines, growth factors, lipids, and oxidative products. IL-5 is critical for the differentiation, migration, activation, and survival of eosinophils but is also implicated in the biological functions of mast cells, basophils, innate lymphoid cells, B cells, and epithelial cells. Results from clinical trials of therapeutics that target type 2 inflammatory mediators (including but not limited to anti-IL-5, anti-immunoglobulin-E, and anti-IL-4/13) may provide further evidence of how eosinophils and IL-5 contribute to CRSwNP. Finally, the association between eosinophilia/elevated IL-5 and greater rates of NP recurrence after endoscopic sinus surgery (ESS) suggests that these mediators may have utility as biomarkers of NP recurrence in diagnosing and assessing the severity of CRSwNP. This review provides an overview of eosinophil and IL-5 biology and explores the literature regarding the role of these mediators in CRSwNP pathogenesis and NP recurrence following ESS. Based on current published evidence, we suggest that although eosinophils play a key role in CRSwNP pathophysiology, IL-5, a cytokine that activates these cells, also represents a pertinent and effective treatment target in patients with CRSwNP.

Keywords: antibodies; biological products; biomarkers; cytokines; immunity; inflammation; innate; monoclonal; nasal obstruction.

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Conflict of interest statement

Philippe Gevaert has participated in advisory boards and received speaker fees from ALK‐Abelló, Argenx, AstraZeneca, Genentech, GSK, Novartis, Regeneron, Roche, Sanofi Genzyme, and Stallergenes‐Greer; Joseph K. Han has received consultancy fees from Sanofi Genzyme, Regeneron, Genentech, AstraZeneca, GSK, and Gossamer Bio; Steven G. Smith, Ana R. Sousa, Peter H. Howarth, Steven W. Yancey, and Robert Chan are employees of GSK and own stocks/shares; Claus Bachert has participated in advisory boards and received speaker fees from Sanofi, Novartis, AstraZeneca, GlaxoSmithKline, ALK‐Abelló, and Meda Pharmaceuticals.

Figures

FIGURE 1
FIGURE 1
IL‐5 regulation of IL‐5Rα isoforms., IL‐5 promotes eosinophil activation and survival and reduces the responsiveness of eosinophils to IL‐5 by regulating expression of the soluble and transmembrane IL‐5Rα isoforms. mRNA, messenger ribonucleic acid; sol‐IL‐5Rα, soluble interleukin‐5 alpha receptor; TM‐IL‐5Rα; transmembrane interleukin‐5 alpha receptor
FIGURE 2
FIGURE 2
Type 2 inflammatory mediators and biologic therapies targeting type 2 inflammation in CRSwNP., , , , , , , , , , , CRSwNP, chronic rhinosinusitis with nasal polyps; Ig, immunoglobin; IL, interleukin; ILC2, group 2 innate lymphoid cell; Th, T helper
FIGURE 3
FIGURE 3
The role of IL‐5 and eosinophils in the pathophysiology of CRSwNP., , , , , , , , , , , , , CLC, Charcot–Leyden crystals; CRSwNP, chronic rhinosinusitis with nasal polyps; DNA, deoxyribonucleic acid; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; Ig, immunoglobulin; IL, interleukin; ILC2, group 2 innate lymphoid cell; LTC4, leukotriene C4; LTD4, leukotriene D4; LTE4, leukotriene E4; NGF, nerve growth factor; O2−•, superoxide radical anion; PAF, platelet‐activating factor
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