Clinical Characteristics and Expression Pattern of IL-33 and IL-25 According to Histologic Classification in Chronic Rhinosinusitis with Nasal Polyposis

Ha Kim Sung; Ji-Hun Mo; Jun Chung Young; Jun Xu; Jae Park Sung; Ki-Sang Rha; Min Kim Yong

doi:10.18787/jr.2015.22.1.18

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Sung, Mo, Young, Xu, Sung, Rha, and Yong: Clinical Characteristics and Expression Pattern of IL-33 and IL-25 According to Histologic Classification in Chronic Rhinosinusitis with Nasal Polyposis

Original Article

J Rhinol 2015;22(1):18-27.

Published online: 10 January 2015

DOI: https://doi.org/10.18787/jr.2015.22.1.18

Clinical Characteristics and Expression Pattern of IL-33 and IL-25 According to Histologic Classification in Chronic Rhinosinusitis with Nasal Polyposis

Ha Kim Sung, MD¹, Ji-Hun Mo, MD², Jun Chung Young, MD², Jun Xu, MD¹, Jae Park Sung, MD¹, Ki-Sang Rha, MD¹, Min Kim Yong, MD^1,

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon;

² Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University School of Medicine, Chonan, Korea

교신저자：김용민, 301-721 대전광역시 중구 문화로 282충남대학교 의학전문대학원 이비인후과학교실, 의학연구소 Tel: +82-42-280-7696, Fax: +82-42-253-4059 E-mail: entkym@cnu.ac.kr

Received 14 January 2015 Revised 10 March 2015 Accepted 18 May 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Objectives

Many kinds of inflammatory cells and cytokines are suggested to be related to the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP), but not yet fully understood. The objectives of this study were to classify CRSwNP patients according to histologic features and to reveal the roles of IL-33 and IL-25, on the pathophysiology of CRSwNP. Materials and Method： CRSwNP patients (n=122) were divided into 3 groups according to the type of nasal polyp; eosinophilic polyp (EP, n=38), neutrophilic polyp (NeuP, n=15) and non-eosinophilic non-neutrophilic polyp (NENN, n=63) groups. Clinical features and the expressions of IL-25 and IL-33 were evaluated among the groups. Results： The EP group showed many clinical features that were different from the other groups: increased prevalence of asthma and olfactory dysfunction, increased percentage of blood eosinophils, increased E/M ratio, and poor postoperative outcomes such as recurrent polyposis and the need for frequent use of oral steroids. Numbers of IL-33 and IL-25 positive cells were significantly higher in the EP group compared with the other groups in the lamina propria (p=0.001). Conclusion： These results suggest that patients with an eosinophilic polyp are clinically and pathogenetically different from patients with other types of polyps, and IL-25 and IL-33 are associated with the pathogenesis of chronic rhinosinusitis with eosinophilic polyps.

Keywords: Nasal polyps, Sinusitis, Eosinophil, IL-25, IL-33.

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Fig. 1.

Representative CT findings of ethmoid sinus domiant & maxillary sinus dominant CRSwNP.

Fig. 2.

Classification of patients with chronic rhinosinusitis with nasal polyposis according to the histopathologic feature of the nasal polyp. A: Control. B: EP. C: NP. D: NENP. H&E stain (×400). Scale bar: 20 µm. EP: eosinophilic polyp. NP: neutrophilic polyp. NENP: non-eosinophilic & non-neutrophilic polyp.

Fig. 3.

Correlation of blood eosinophil differential count and infiltrated eosinophil number of nasal polyps (A) and Relationship of infiltrated eosinophil number of nasal polyp and Lund-MacK-ay score (B) in patients with eosinophilic nasal polyp.

Fig. 4.

Expression patterns of IL-33 among the groups. Immunohistochemical stain was performed to detect of IL-33 expression in the tissues. A: Isotype control. B: Control group. C: EP. D: NP. E: NENP. IL-33 positive cells were count in the epithelium (F) and subepithelium (G). Immunohistochemical staining (×400). Scale bar: 20 µm. *: p＜0.05 compared with other groups, †: p＜0.05 compared with contol group. EP: eosinophilic polyp. NP: neutrophilic polyp. NENP: non-eosinophilic, & non-neutrophilic polyp.

Fig. 5.

Expression patterns of IL-25 among the groups. Immunohistochemical stain was performed to detect of IL-25 expression in the tissues. A: Isotype control. B: Control group. C: EP. D: NP. E: NENP. IL-25 positive cells were count in the epithelium (F) and subepithelium (G). Immunohistochemical staining (×400). Scale bar: 20 µm. *: p＜0.05 compared with other groups, †: p＜0.05 compared with contol group. EP: eosinophilic polyp, NP: neutrophilic polyp, NENP: non-osinophilic & non-neutrophilic polyp.

Table 1.

Patients characteristics

	Control (n=6)	EP (n=38)	NP (n=15)	NENP (n=63)
Sex, male, n (%)	4 (66.7)	22 (57.8)	12 (80)	44 (69.8)
Age, mean± SD	44.5±18.2	4.2±13.7	44.1±16.1	42.7±17.0
Asthma, n (%)	0	07 (18.5)^*	01 (6.7)	03 (4.5)
Allergic rhinitis, n (%)	0	05 (13.2)	02 (13.3)	07 (11.1)

^* p＜0.05 compared with other groups. EP: eosinophilic polyp, NP: neutrophilic polyp, NENP: non-eosinophilic & non-neutrophilic polyp

Table 2.

Clinical features of patients

	Control	EP	NP	NENP
Olfactory dysfunction, n (%)	0	32 (84.2)^*	8 (53.3)	47 (69.1)
Blood eosinophil (%)	1.67±1.4	6.8±3.3^**	2.1±1.5	3.2±1.7
Lund-kennedy endoscopic score	0	2.9±1.0	2.8±1.3	3.3±1.2
Lund-mackay CT score	0	13.7±3.8	12.5±3.9	15.9±5.2
E/M ratio
Total	–	1.77±0.8^**	0.8±0.2	0.9±0.3
Rt	–	1.7±0.7^*	0.8±0.2	0.9±0.3
Lt	–	1.88±0.2^**	0.8±0.2	0.9±0.3

^* p＜0.05 compared with other groups

^** p＜0.001 compared with other groups. EP: eosinophilic polyp, NP: neutrophilic polyp, NENP: non-eosinophilic & non-neutrophilic polyp, E/M ratio: E thmoid/Maxillay ratio of modified Lund-Mackay CT score and this ratio was calculated from unilateral side

Table 3.

Post-operative outcomes of patients

	EP	NP	NENP
Recurrent polyposis, n (%)	11 (29)^*	2 (13.4)	4 (5.9)
Oral steroid therapy, n (%)	12 (31.6)^*	1 (6.7)	4 (5.9)
Revision surgery, n (%)	–	–	2 (3.2)

^* p＜0.05, compared with other groups. EP: eosinophilic polyp, NP: neutrophilic polyp, NENP: non-eosinophilic & non-neutrophilic polyp

Table 4.

Number of IL-33 and IL-25 positive cells in the epithelium and subepithelium among the groups. Mean±SD/HPF (×400)

		Control	EP	NP	NENP
IL-33	Epithelium	38.0±9.3	40.9±9.2	46.2±8.8	39.3±8.2
	Sub-epithelium	19.0±7.6	70.0±10.8^*	45.1±15.9^†	43.6±13.5^†
IL-25	Epithelium	26.3±8.1	32.4±8.7	34.6±8.7	28.9±10.1
	Sub-epithelium	14.5±4.6	60±11.5^*	37.3±13.0^†	43.5±14.6^†

^* p＜0.05 compared with other groups

^† p＜0.05 compared with contol group. EP: eosinophilic polyp, NP: neutrophilic polyp, NENP: non-eosinophilic & non-neutrophilic polyp

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