Table 1.

Role of eosinophil activating mediators and compounds from eosinophil specific granules in intestinal inflammation.

	Pre-clinical evidence	Clinical evidence
IL-4	◊ IL-4 blocking in IL-10 deficient mice: protected from colitis development (63) ◊ No IL-4Rα: no disease development (73)	◊ UC patients: ↑ IL-4 expression levels in inflamed mucosa (62) ◊ CD patients: ↓ IL-4 levels in intestinal tissue due to lower numbers of IL-4 producing cells in mucosal biopsies (74)
	◊ IL-4/IL-13 dual antagonist in oxazolone colitis model (67, 68)  - Reduced overall disease activity ◊ IL-4/IL-13 blocking trough a shared receptor (69, 71) - Reduced overall disease severity
IL-13		◊ CD and UC patients: ↑ IL-13Rα2 in mucosal biopsies (94, 95) ◊ Potential biomarker for anti-TNF non-responsiveness (96) ◊ Clinical trial with Tralokinumab and Anrukinzumab: no therapeutic effects (62)
	◊ {IL-13Rα2 KO model     IL-13Rα2 antibody mediated depletion   DSS model: mice protected ssssss from colitis introduction (92) ◊ IL-13Rα2 KO model: not protected from colitis development but recovered faster (91)
IL-5		◊ {Mepolizumab & Reslizumab   Benralizumab   Attenuates type 2 response + used and shown effective in eosnophl   eosinophilic asthma patients ◊ UC patients’ rectal perfusion fluids (84):  - ↑ IL-5 levels
IL-33	◊ SAMP/YitFc colitis model and antibody mediated ST2 blocking (102):  - ↓ Th2 cytokine production and ↓ eosinophil recruitment into the ileum ◊ C57BL/6 ST2 KO mice (104) and ST2 antibody mediated depletion in C57BL/6 mice alleviated disease symptoms	◊ UC patients: ↑ colonic IL-33 mRNA levels and activated eosinophils (100) ◊ IBD patients’ intestinal biopsies (101–103):  - ST2/IL-33 signaling  - Eosinophil infiltration which coincided with Th2 mediated immune response  - IL-4, IL-5 and IL-13 release
TGF-β1	◊ TGF-β1 deficient mice: spontaneously develop colitis (113, 114)	◊ Active inflammation in IBD patients:  ↑  }TGF-β1 protein levels  ↓  (111, 112)  =
EDN		◊ UC patients: ↑ f(EDN) protein levels during and 3 months prior to relapse: possible prognostic role (131) ◊ Suggested as a prognostic marker in paediatric patients (132)
ECP		◊ Active CD and UC: ↑ serum ECP compared to HC (118)
		◊ Eosinophil gastroenteritis: ECP and MBP deposition in small bowel (119)
MBP	◊ MBP KO mice: no colitis development upon oxazolone exposure (135) ◊ In vitro co-culture of eosinophils and epithelial cells decreased functioning of the epithelial barrier  - attributed to MBP (135)
		◊ MBP directly increases epithelial layer permeability via its toxicity (134)
EPX	◊ DSS colitis model: ↑ EPX release in colonic lumen (130) ◊ EPX-/- mice: colitis amelioration (130)	◊ CD patients’ colonic mucosal biopsies and UC patients’ colonic perfusion fluids  - ↑ EPX levels during active disease (123–125) ◊ IBD patients: EPX ↑ at diagnosis but decreased again during disease course (126)