The Role of T Helper Type 2 (Th2) Cytokines in the Pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (eGPA): an Illustrative Case and Discussion

Curr Allergy Asthma Rep. 2022 Nov;22(11):141-150. doi: 10.1007/s11882-022-01039-w. Epub 2022 Sep 14.

Abstract

Purposeof review: The pathogenesis of eosinophilic granulomatosis with polyangiitis (eGPA) is driven largely by CD4 + type 2 helper T cells (Th2), B cells, and eosinophils. Interleukin (IL)-4 and IL-13 are critical cytokines in Th2 cell-mediated inflammation; however, inhibition of IL-4 and IL-13 does not reduce serum eosinophil counts and has even been associated with hypereosinophilia. This review explores the role of IL-4, IL-5, and IL-13 in Th2-mediated inflammation to consider the potential clinical consequences of inhibiting these individual cytokines in eGPA.

Recent findings: Treatments for eosinophilic granulomatosis with polyangiitis (eGPA) are rapidly evolving through using biologic therapies to modulate the Th2 inflammatory response via eosinophil inhibition. While IL-4, IL-5, IL-13, and IL-25 can all affect eosinophils, only IL-5 inhibition has demonstrated therapeutic benefit to-date. In this review, we report a clinical vignette of a patient with adult-onset asthma who developed severe manifestations of eGPA after switching from mepolizumab (an IL-5 inhibitor) to dupilumab (an inhibitor of IL-4 and IL-13). By understanding the role of IL-4, IL-5, and IL-13 in Th2-mediated vasculitis, we can start to understand how eGPA might respond differently to focused cytokine inhibition.

Keywords: Eosinophilic granulomatosis with polyangiitis; IL-13; IL-4; IL-5; Th2 inflammatory response.

Publication types

  • Review

MeSH terms

  • Adult
  • Churg-Strauss Syndrome* / complications
  • Churg-Strauss Syndrome* / drug therapy
  • Cytokines
  • Granulomatosis with Polyangiitis* / drug therapy
  • Humans
  • Inflammation
  • Interleukin-13 / therapeutic use
  • Interleukin-4 / therapeutic use
  • Interleukin-5
  • Th2 Cells

Substances

  • Cytokines
  • Interleukin-13
  • Interleukin-5
  • Interleukin-4