Comparison of the Nasal Release of IL-4,IL-10,IL-17,CCL13/MCP-4,and CCL26/eotaxin-3 in Allergic Rhinitis during Season and after Allergen Challenge

Abstract

Background

Allergic rhinitis is an inflammatory disease characterized by local overproduction of type 2 cytokines and tissue eosinophilia. Recent research suggests the involvement of additional cytokines such as IL-17, chemokine (C-C motif) ligand (CCL) 26/eotaxin-3, and CCL13/monocyte chemoattractant protein-4 (MCP-4) in its pathophysiology. Furthermore, bronchial epithelial cells treated with IL-17 and type 2 cytokines distinctively up-regulated eotaxin-3 gene expression. In this study we investigated the kinetics of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in seasonal allergic rhinitis volunteers after nasal allergen challenge (NAC) and their release during natural pollen exposure.

Methods

The nasal lavages of 15 symptomatic allergic and 14 nonallergic subjects were collected during the pollination season. Additionally, six allergic subjects underwent a single unilateral nasal allergen and control challenge out of season, and nasal secretions were collected. Levels of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in nasal lavages and secretions were measured using an electrochemiluminescent assay.

Results

After NAC, allergic subjects had a significant immediate response of nasal symptoms as well as a significant increase at 5 hours of IL-4, IL-10, and IL-17 and at 2, 5, and 24 hours significantly raising levels of eotaxin-3. IL-17 and eotaxin-3 concentrations at 5 hours were correlated (r = 0.94; p = 0.005). During natural pollen exposure, barely detectable levels of IL-17 in allergic subjects were also correlated with eotaxin-3 (r = 0.62; p = 0.01). Eotaxin-3 and MCP-4 levels were significantly elevated 9- or 3.7-fold, respectively, and IL-10 and, unexpectedly, IL-4 were significantly lower in allergic subjects compared with nonallergic subjects.

Conclusion

Nasal IL-17, MCP-4, and, possibly, eotaxin-3 may aggravate and IL-10 may alleviate nasal mucosal allergy.

Get full access to this article

View all access options for this article.

References

Broide

D.H.

Allergic rhinitis: Pathophysiology.

Allergy Asthma Proc 31: 370–374, 2010.

Uzzaman

A.A.

and Story

R.R.

Chapter 5: Allergic rhinitis.

Allergy Asthma Proc 33(suppl 1): 15–18, 2012.

Bousquet

Khaltaev

Cruz

A.A.

Allergic Rhinitis and Its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen).

Allergy 63(suppl 86): 8–160, 2008.

Feng

C.H.

Miller

M.D.

and Simon

R.A.

The united allergic airway: Connections between allergic rhinitis, asthma, and chronic sinusitis.

Am J Rhinol Allergy 26: 187–190, 2012.

Marple

B.F.

Allergic rhinitis and inflammatory airway disease: Interactions within the unified airspace.

Am J Rhinol Allergy 24: 249–254, 2010.

Blaiss

M.S.

Allergic rhinitis: Direct and indirect costs.

Allergy Asthma Proc 31: 375–380, 2010.

Holgate

S.T.

and Polosa

Treatment strategies for allergy and asthma.

Nat Rev Immunol 8: 218–230, 2008.

Akdis

C.A.

Blesken

Akdis

Role of interleukin 10 in specific immunotherapy.

J Clin Invest 102: 98–106, 1998.

Akdis

Burgler

Crameri

Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases.

J Allergy Clin Immunol 127: 701–21.e1-70, 2011.

10.

Zhang

Wang

D.Y.

Opposing roles of IL-17A and IL-25 in the regulation of TSLP production in human nasal epithelial cells.

Allergy 65: 581–589, 2010.

11.

Klemens

Rasp

Jund

Mediators and cytokines in allergic and viral- triggered rhinitis.

Allergy Asthma Proc 28: 434–441, 2007.

12.

Wang

Y.H.

Voo

K.S.

Liu

A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma.

J Exp Med 207: 2479–2491, 2010.

13.

Neill

D.R.

Wong

S.H.

Bellosi

Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.

Nature 464: 1367–1370, 2010.

14.

Wang

Clement

Smitz

Correlations between complaints, inflammatory cells and mediator concentrations in nasal secretions after nasal allergen challenge and during natural allergen exposure.

Int Arch Allergy Immunol 106: 278–285, 1995.

15.

Wagenmann

Schumacher

and Bachert

The time course of the bilateral release of cytokines and mediators after unilateral nasal allergen challenge.

Allergy 60: 1132–1138, 2005.

16.

Boghdadi

Marei

Ali

Immunological markers in allergic rhinitis patients treated with date palm immunotherapy.

Inflamm Res 61: 719–724, 2012.

17.

Benson

Strannegard

I.L.

Wennergren

and Strannegard

Cytokines in nasal fluids from school children with seasonal allergic rhinitis.

Pediatr Allergy Immunol 8: 143–149, 1997.

18.

Chawes

Edwards

Shamji

A novel method for assessing unchallenged levels of mediators in nasal epithelial lining fluid.

J Allergy Clin Immunol 125: 1387–1389.e3, 2010.

19.

Quan

S.H.

Zhang

Y.L.

Han

D.H.

Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model.

Ann Allergy Asthma Immunol. 108: 342–350, 2012.

20.

Ciprandi

De Amici

Murdaca

Serum interleukin-17 levels are related to clinical severity in allergic rhinitis.

Allergy 64: 1375–1378, 2009.

21.

Chae

S.C.

Park

Y.R.

G.J.

The suggestive association of eotaxin-2 and eotaxin-3 gene polymorphisms in Korean population with allergic rhinitis.

Immunogenetics 56: 760–764, 2005.

22.

Wang

Zhang

Han

and Zhang

Association between polymorphisms in cytokine genes IL-17A and IL-17F and development of allergic rhinitis and comorbid asthma in Chinese subjects.

Hum Immunol 73: 647–653, 2012.

23.

Mendez-Enriquez

Melendez

Martinez

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation.

Clin Exp Immunol 152: 354–363, 2008.

24.

Zhang

R.X.

S.Q.

Jiang

J.Z.

and Liu

G.J.

Complementary DNA microarray analysis of chemokines and their receptors in allergic rhinitis.

J Investig Allergol Clin Immunol 17: 329–336, 2007.

25.

Carr

T.F.

and Saltoun

C.A.

Chapter 2: Skin testing in allergy.

Allergy Asthma Proc 33: 6–8, 2012.

26.

Conover

W.J.

Chapter 5: Some methods based on ranks. Section 5.8 Several related samples - The Friedman test. In Practical Nonparametric Statistics. New York: Wiley, 369–373, 1999.

27.

Milovanovic

Drozdenko

Weise

Interleukin-17A promotes IgE production in human B cells.

J Invest Dermatol 130: 2621–2628, 2010.

28.

Rodriguez

F.H.

Kanaly

Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense.

J Exp Med 194: 519–527, 2001.

29.

Nakae

Komiyama

Nambu

Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses.

Immunity 17: 375–387, 2002.

30.

Ciprandi

Filaci

and Fenoglio

Th17 cells and allergic rhinitis: Is there clinical relevance?

Otolaryngol Head Neck Surg 143: 604–605, 2010.

31.

Kitaura

Suzuki

Imai

Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3.

J Biol Chem 274: 27975–27980, 1999.

32.

Semik-Orzech

Barczyk

Wiaderkiewicz

and Pierzchała

Eotaxin, but not IL-8, is increased in upper and lower airways of allergic rhinitis subjects after nasal allergen challenge.

Allergy Asthma Proc 32: 230–238, 2011.

33.

Berkman

Ohnona

Chung

and Breuer

Eotaxin-3 but not eotaxin gene expression is upregulated in asthmatics 24 hours after allergen challenge.

Am J Respir Cell Mol Biol 24: 682–687, 2001.

34.

Ogilvie

Paoletti

Clark-Lewis

and Uguccioni

Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes.

Blood 102: 789–794, 2003.

35.

Petkovic

Moghini

Paoletti

Eotaxin-3/CCL26 is a natural antagonist for CC chemokine receptors 1 and 5. A human chemokine with a regulatory role.

J Biol Chem 279: 23357–23363, 2004.

36.

Wright

E.D.

Christodoulopoulos

Small

Th-2 type cytokine receptors in allergic rhinitis and in response to topical steroids.

Laryngoscope 108: 1528–1533, 1998.

37.

Pouliot

Turmel

Gélinas

Interleukin-4 production by human alveolar macrophages.

Clin Exp Allergy 35: 804–810, 2005.

38.

Vasiliev

A.M.

Vasilenko

R.N.

Kulikova

N.L.

Structural and functional properties of IL-4delta2, an alternative splice variant of human IL-4.

J Proteome Res 2: 273–281, 2003.

39.

Glare

E.M.

Divjak

Rolland

J.M.

and Walters

E.H.

Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4delta2.

J Allergy Clin Immunol 104: 978–982, 1999.

40.

Yadav

Govindasamy

G.K.

and Naidu

Polymorphic variants of interleukin-13 R130Q, interleukin-4 T589C, interleukin-4RA I50V, and interleukin-4RA Q576R in allergic rhinitis: A pilot study.

Allergy Rhinol (Providence) 3: e35–e40, 2012.

41.

Chen

and Qin

Paradoxical roles of IL-4 in tumor immunity.

Cell Mol Immunol 6: 415–422, 2009.

42.

M.P.

Chen

R.X.

Wang

M.L.

Association study on IL4, IL13 and IL4RA polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population.

PLoS ONE 6: e27363, 2011.

43.

de Guia

R.M.

and Ramos

J.D.

The –590C/TIL4 single-nucleotide polymorphism as a genetic factor of atopic allergy.

Int J Mol Epidemiol Genet 1: 67–73, 2010.

44.

Jeannin

Lecoanet

Delneste

IgE versus IgG4 production can be differentially regulated by IL-10.

J Immunol 160: 3555–3561, 1998.

45.

Takanaski

Nonaka

Xing

Interleukin 10 inhibits lipopolysaccharide- induced survival and cytokine production by human peripheral blood eosinophils.

J Exp Med 180: 711–715, 1994.

46.

Enk

A.H.

Angeloni

V.L.

Udey

M.C.

and Katz

S.I.

Inhibition of Langerhans cell antigen-presenting function by IL-10. A role for IL-10 in induction of tolerance.

J Immunol 151: 2390–2398, 1993.

47.

Meiler

Zumkehr

Klunker

In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure.

J Exp Med. 205: 2887–2898, 2008.

48.

Hussein

P.Y.

Zahran

Ashour Wahba

Interleukin 10 receptor alpha subunit (IL-10RA) gene polymorphism and IL-10 serum levels in Egyptian atopic patients.

J Investig Allergol Clin Immunol 20: 20–26, 2010.

49.

Benson

Strannegard

I.L.

Wennergren

and Strannegard

Increase of the soluble IL-4 receptor (IL-4sR) and positive correlation between IL-4sR and IgE in nasal fluids from school children with allergic rhinitis.

Allergy Asthma Proc 21: 89–95, 2000.

50.

KleinJan

Dijkstra

M.D.

Boks

S.S.

Increase in IL-8, IL-10, IL-13, and RANTES mRNA levels (in situ hybridization) in the nasal mucosa after nasal allergen provocation.

J Allergy Clin Immunol 103: 441–450, 1999.