Cytokine Profiles in Allergic Rhinitis

RHINITIS (JJ OPPENHEIMER AND J CORREN, SECTION EDITORS)
Part of the following topical collections:
  1. Topical Collection on Rhinitis

Abstract

Allergic rhinitis, particularly seasonal allergic rhinitis, is considered a classic Th2-mediated disease, with important contributions to pathology by interleukins 4, 5 and 13. As such, allergic rhinitis is an excellent model for studying allergic inflammation, with findings potentially relevant to the mechanism of lower airways inflammation seen in allergic asthma. However, recent evidence has revealed roles for additional non-Th2 cytokines in asthma, including IL-17 family cytokines and epithelial-derived cytokines. Additionally, putative roles for epithelial-derived cytokines and innate lymphoid cells have been described in chronic rhinosinusitis with nasal polyps. Here, evidence for the involvement of different cytokines and cytokine groups in allergic rhinitis is considered.

Keywords

Allergic rhinitis Cytokine Cytokine profile Interleukin Th2 IL-17 TSLP IL-33 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Maes T, Joos GF, Brusselle GG. Targeting interleukin-4 in asthma: lost in translation? Am J Respir Cell Mol Biol. 2012;47(3):261–70.CrossRefPubMedGoogle Scholar
  2. 2.
    Cosmi L, Liotta F, Maggi E, Romagnani S, Annunziato F. Th17 cells: new players in asthma pathogenesis. Allergy. 2011;66(8):989–98.CrossRefPubMedGoogle Scholar
  3. 3.
    Ying S, O'Connor B, Ratoff J, Meng Q, Fang C, Cousins D, et al. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J Immunol. 2008;181(4):2790–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Lloyd CM. IL-33 family members and asthma – bridging innate and adaptive immune responses. Curr Opin Immunol. 2010;22(6):800–6.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Scadding GW, Calderon MA, Bellido V, Koed GK, Nielsen NC, Lund K, et al. Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes. J Immunol Methods. 2012;384(1–2):25–32.CrossRefPubMedGoogle Scholar
  6. 6.
    Castells M, Schwartz LB. Tryptase levels in nasal-lavage fluid as an indicator of the immediate allergic response. J Allergy Clin Immunol. 1988;82(3 Pt 1):348–55.CrossRefPubMedGoogle Scholar
  7. 7.
    Riechelmann H, Deutschle T, Friemel E, et al. Biological markers in nasal secretions. Eur Respir J. 2003;21(4):600–5.CrossRefPubMedGoogle Scholar
  8. 8.
    Kitamura Y, Mizuguchi H, Ogishi H, Kuroda W, Hattori M, Fukui H, et al. Preseasonal prophylactic treatment with antihistamines suppresses IL-5 but not IL-33 mRNA expression in the nasal mucosa of patients with seasonal allergic rhinitis caused by Japanese cedar pollen. Acta Otolaryngol. 2012;132(4):434–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Nouri-Aria KT, O'Brien F, Noble W, et al. Cytokine expression during allergen-induced late nasal responses: IL-4 and IL-5 mRNA is expressed early (at 6 h) predominantly by eosinophils. Clin Exp Allergy. 2000;30(12):1709–16.CrossRefPubMedGoogle Scholar
  10. 10.
    Xu G, Zhang L, Wang DY, Xu R, Liu Z, Han DM, et al. Opposing roles of IL-17A and IL-25 in the regulation of TSLP production in human nasal epithelial cells. Allergy. 2010;65(5):581–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Till S, Durham S, Dickason R, Huston D, Bungre J, Walker S, et al. IL-13 production by allergen-stimulated T cells is increased in allergic disease and associated with IL-5 but not IFN-gamma expression. Immunology. 1997;91(1):53–7.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.•
    Pilette C, Jacobson MR, Ratajczak C, Detry B, Banfield G, VanSnick J, et al. Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis. Allergy. 2013;68(3):312–21. Alterations in dendritic cell function in allergic rhinitis demonstrated both locally in the nasal mucosa and in the peripheral circulation. CrossRefPubMedGoogle Scholar
  13. 13.
    Sakashita M, Yoshimoto T, Hirota T, Harada M, Okubo K, Osawa Y, et al. Association of serum interleukin-33 level and the interleukin-33 genetic variant with Japanese cedar pollinosis. Clin Exp Allergy. 2008;38(12):1875–81.CrossRefPubMedGoogle Scholar
  14. 14.
    Cameron LA, Durham SR, Jacobson MR, Masuyama K, Juliusson S, Gould HJ, et al. Expression of IL-4, Cepsilon RNA, and Iepsilon RNA in the nasal mucosa of patients with seasonal rhinitis: effect of topical corticosteroids. J Allergy Clin Immunol. 1998;101(3):330–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Patel D, Couroux P, Hickey P, Salapatek AM, Laidler P, Larché M, Hafner RP. Fel d 1-derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: a randomized, placebo-controlled study. J Allergy Clin Immunol. 2013;131(1):103-9.e1-7Google Scholar
  16. 16.
    Reinartz SM, van Ree R, Versteeg SA, Zuidmeer L, van Drunen CM, Fokkens WJ. Diminished response to grass pollen allergen challenge in subjects with concurrent house dust mite allergy. Rhinology. 2009;47(2):192–8.PubMedGoogle Scholar
  17. 17.
    Kikuchi Y, Takai T, Kuhara T, Ota M, Kato T, Hatanaka H, et al. Crucial commitment of proteolytic activity of a purified recombinant major house dust mite allergen Der p1 to sensitization toward IgE and IgG responses. J Immunol. 2006;177(3):1609–17.CrossRefPubMedGoogle Scholar
  18. 18.
    Naclerio RM, Proud D, Togias AG, Adkinson Jr NF, Meyers DA, Kagey-Sobotka A, et al. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med. 1985;313(2):65–70.CrossRefPubMedGoogle Scholar
  19. 19.
    Creticos PS, Peters SP, Adkinson Jr NF, Naclerio RM, Hayes EC, Norman PS, et al. Peptide leukotriene release after antigen challenge in patients sensitive to ragweed. N Engl J Med. 1984;310(25):1626–30.CrossRefPubMedGoogle Scholar
  20. 20.
    Mosimann BL, White MV, Hohman RJ, Goldrich MS, Kaulbach HC, Kaliner MA. Substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide increase in nasal secretions after allergen challenge in atopic patients. J Allergy Clin Immunol. 1993;92(1 Pt 1):95–104.CrossRefPubMedGoogle Scholar
  21. 21.
    Erin EM, Zacharasiewicz AS, Nicholson GC, Tan AJ, Higgins LA, Williams TJ, et al. Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge. Clin Exp Allergy. 2005;35(12):1608–14.CrossRefPubMedGoogle Scholar
  22. 22.
    Wagenmann M, Schumacher L, Bachert C. The time course of the bilateral release of cytokines and mediators after unilateral nasal allergen challenge. Allergy. 2005;60(9):1132–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Linden M, Svensson C, Andersson E, Andersson M, Greiff L, Persson CG. Immediate effect of topical budesonide on allergen challenge-induced nasal mucosal fluid levels of granulocyte-macrophage colony-stimulating factor and interleukin-5. Am J Respir Crit Care Med. 2000;162(5):1705–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Erin EM, Leaker BR, Zacharasiewicz AS, et al. Single dose topical corticosteroid inhibits IL-5 and IL-13 in nasal lavage following grass pollen challenge. Allergy. 2005;60(12):1524–9.CrossRefPubMedGoogle Scholar
  25. 25.•
    Nicholson GC, Kariyawasam HH, Tan AJ, et al. The effects of an anti-inflammatory IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge. J Allergy Clin Immunol. 2011;128(4):800–7. Systemic administration of anti-IL-13 blocking antibody reduces nasal fluid IL-13 after nasal allergen challenge. CrossRefPubMedGoogle Scholar
  26. 26.
    Bensch GW, Nelson HS, Borish LC. Evaluation of cytokines in nasal secretions after nasal antigen challenge: lack of influence of antihistamines. Ann Allergy Asthma Immunol. 2002;88(5):457–62.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Sim TC, Reece LM, Hilsmeier KA, Grant JA, Alam R. Secretion of chemokines and other cytokines in allergen-induced nasal responses: inhibition by topical steroid treatment. Am J Respir Crit Care Med. 1995;152(3):927–33.CrossRefPubMedGoogle Scholar
  28. 28.
    Terada N, Hamano N, Kim WJ, Hirai K, Nakajima T, Yamada H, et al. The kinetics of allergen-induced eotaxin level in nasal lavage fluid: its key role in eosinophil recruitment in nasal mucosa. Am J Respir Crit Care Med. 2001;164(4):575–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Benson M, Strannegård IL, Wennergren G, Strannegård O. Cytokines in nasal fluids from school children with seasonal allergic rhinitis. Pediatr Allergy Immunol. 1997;8(3):143–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Chawes BL, Edwards MJ, Shamji B, Walker C, Nicholson GC, Tan AJ, et al. A novel method for assessing unchallenged levels of mediators in nasal epithelial lining fluid. J Allergy Clin Immunol. 2010;125(6):1387–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Klemens C, Rasp G, Jund F, Hilgert E, Devens C, Pfrogner E. Kramer MF Mediators and cytokines in allergic and viral-triggered rhinitis. Allergy Asthma Proc. 2007;28(4):434–41.CrossRefPubMedGoogle Scholar
  32. 32.
    Baumann R, Rabaszowski M, Stenin I, Tilgner L, Scheckenbach K, Wiltfang J, et al. 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. Am J Rhinol Allergy. 2013;27(4):266–72.CrossRefPubMedGoogle Scholar
  33. 33.
    Masuyama K, Till SJ, Jacobson MR, Kamil A, Cameron L, Juliusson S, et al. Nasal eosinophilia and IL-5 mRNA expression in seasonal allergic rhinitis induced by natural allergen exposure: effect of topical corticosteroids. J Allergy Clin Immunol. 1998;102(4 Pt 1):610–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Kita H, Jorgensen RK, Reed CE, Dunnette SL, Swanson MC, Bartemes KR, et al. Mechanism of topical glucocorticoid treatment of hay fever: IL-5 and eosinophil activation during natural allergen exposure are suppressed, but IL-4, IL-6, and IgE antibody production are unaffected. J Allergy Clin Immunol. 2000;106(3):521–9.CrossRefPubMedGoogle Scholar
  35. 35.
    KleinJan A, Dijkstra MD, Boks SS, Severijnen LA, Mulder PG, Fokkens WJ. 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. 1999;103(3 Pt 1):441–50.CrossRefPubMedGoogle Scholar
  36. 36.
    Nouri-Aria KT, Pilette C, Jacobson MR, Watanabe H, Durham SR. IL-9 and c-Kit + mast cells in allergic rhinitis during seasonal allergen exposure: effect of immunotherapy. J Allergy Clin Immunol. 2005;116(1):73–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Liu W, Xia W, Fan Y, Wang H, Zuo K, Lai Y, et al. Elevated serum osteopontin level is associated with blood eosinophilia and asthma comorbidity in patients with allergic rhinitis. J Allergy Clin Immunol. 2012;130(6):1416–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Ciprandi G. Serum interleukin 9 in allergic rhinitis. Ann Allergy Asthma Immunol. 2010;104(2):180–1.CrossRefPubMedGoogle Scholar
  39. 39.
    Ying XJ, Zhao SW, Wang GL, Xie J, Xu HM, Dong P. Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: a meta-analysis. Gene. 2013;521(2):222–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Movahedi M, Amirzargar AA, Nasiri R, Hirbod-Mobarakeh A, Farhadi E, Tavakol M, et al. Gene polymorphisms of Interleukin-4 in allergic rhinitis and its association with clinical phenotypes. Am J Otolaryngol. 2013;34(6):676–81.CrossRefPubMedGoogle Scholar
  41. 41.
    Ying X, Zhang R, Yu S, Wu J, Wang H. Association of interleukin-13 SNP rs1800925 with allergic rhinitis risk: a meta-analysis based on 1,411 cases and 3169 controls. Gene. 2012;506(1):179–83.CrossRefPubMedGoogle Scholar
  42. 42.
    Miyake Y, Tanaka K, Arakawa M. Polymorphisms in the IL4 gene, smoking, and rhinoconjunctivitis in Japanese women: the Kyushu Okinawa Maternal and Child Health Study. Hum Immunol. 2012;73(10):1046–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Gröger M, Klemens C, Wendt S, Becker S, Canis M, Havel M, et al. Mediators and cytokines in persistent allergic rhinitis and nonallergic rhinitis with eosinophilia syndrome. Int Arch Allergy Immunol. 2012;159(2):171–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Verhaeghe B, Gevaert P, Holtappels G, Lukat KF, Lange B, Van Cauwenberge P, et al. Up-regulation of IL-18 in allergic rhinitis. Allergy. 2002;57(9):825–30.CrossRefPubMedGoogle Scholar
  45. 45.
    Bachert C, van Kempen M, Van Cauwenberge P. Regulation of proinflammatory cytokines in seasonal allergic rhinitis. Int Arch Allergy Immunol. 1999;118(2–4):375–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Sim TC, Grant JA, Hilsmeier KA, Fukuda Y, Alam R. Proinflammatory cytokines in nasal secretions of allergic subjects after antigen challenge. Am J Respir Crit Care Med. 1994;149(2 Pt 1):339–44.CrossRefPubMedGoogle Scholar
  47. 47.
    Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol. 2001;108(3):430–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol. 2008;122(5):961–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Scadding GW, Eifan A, Penagos M, Koed GK, Shamji MH, Wurtzen PA, Durham SR. Grass pollen nasal challenge is associated with increases in Th2 cytokines, Eotaxin, MDC and IL-6 in nasal fluid; Th1 and Th17-associated cytokines are low and do not increase following challenge. Abstract; EAACI SERIN meeting, Leuven, March 2013.Google Scholar
  50. 50.
    Ciprandi G, Fenoglio D, De Amici M, Quaglini S, Negrini S, Filaci G. Serum IL-17 levels in patients with allergic rhinitis. J Allergy Clin Immunol. 2008;122(3):650–1.CrossRefPubMedGoogle Scholar
  51. 51.
    Bajoriuniene I, Malakauskas K, Lavinskiene S, Jeroch J, Gasiuniene E, Vitkauskiene A, et al. Response of peripheral blood Th17 cells to inhaled Dermatophagoides pteronyssinus in patients with allergic rhinitis and asthma. Lung. 2012;190(5):487–95.CrossRefPubMedGoogle Scholar
  52. 52.
    Liu Y, Yu HJ, Wang N, Zhang YN, Huang SK, Cui YH, et al. Clara cell 10-kDa protein inhibits T(H)17 responses through modulating dendritic cells in the setting of allergic rhinitis. J Allergy Clin Immunol. 2013;131(2):387–94.PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Wang H, Mobini R, Fang Y, Barrenäs F, Zhang H, Xiang Z, et al. Allergen challenge of peripheral blood mononuclear cells from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation. Clin Exp Allergy. 2010;40(8):1194–202.CrossRefPubMedGoogle Scholar
  54. 54.
    Licona-Limón P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol. 2013;14(6):536–42.CrossRefPubMedGoogle Scholar
  55. 55.
    Saglani S, Lui S, Ullmann N, Campbell GA, Sherburn RT, Mathie SA, et al. IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma. J Allergy Clin Immunol. 2013;132(3):676–85.CrossRefPubMedGoogle Scholar
  56. 56.
    Shikotra A, Choy DF, Ohri CM, Doran E, Butler C, Hargadon B, et al. Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. J Allergy Clin Immunol. 2012;129(1):104–11.CrossRefPubMedGoogle Scholar
  57. 57.•
    Shaw JL, Fakhri S, Citardi MJ, Porter PC, Corry DB, Kheradmand F, et al. IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps. Am J Respir Crit Care Med. 2013;188(4):432–9. Elevated levels of ST2+ innate lymphoid cells in ethmoid sinus mucosa in patients with chronic rhinosinusitis with nasal polyps compared to patients with chronic rhinosinusitis without nasal polyps or healthy controls. CrossRefPubMedGoogle Scholar
  58. 58.••
    Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, et al. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol. 2011;12(11):1055–62. Description of a CRTH2+ innate lymphoid cell population in humans with enrichment in nasal polyp tissue. CrossRefPubMedGoogle Scholar
  59. 59.
    Kamekura R, Kojima T, Koizumi J, Ogasawara N, Kurose M, Go M, et al. Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells. Cell Tissue Res. 2009;338(2):283–93.CrossRefPubMedGoogle Scholar
  60. 60.
    Mou Z, Xia J, Tan Y, Wang X, Zhang Y, Zhou B, et al. Overexpression of thymic stromal lymphopoietin in allergic rhinitis. Acta Otolaryngol. 2009;129(3):297–301.CrossRefPubMedGoogle Scholar
  61. 61.
    Zhu DD, Zhu XW, Jiang XD, Dong Z. Thymic stromal lymphopoietin expression is increased in nasal epithelial cells of patients with mugwort pollen sensitive-seasonal allergic rhinitis. Chin Med J (Engl). 2009;122(19):2303–7.Google Scholar
  62. 62.
    Zhang Y, Song X, Zhao Y, Zhang L, Bachert C. Single nucleotide polymorphisms in thymic stromal lymphopoietin gene are not associated with allergic rhinitis susceptibility in Chinese subjects. BMC Med Genet. 2012;13:79.PubMedCentralCrossRefPubMedGoogle Scholar
  63. 63.
    Zhang Y, Wang X, Zhang W, Han D, Zhang L, Bachert C. Polymorphisms in thymic stromal lymphopoietin gene demonstrate a gender and nasal polyposis-dependent association with chronic rhinosinusitis. Hum Immunol. 2013;74(2):241–8.CrossRefPubMedGoogle Scholar
  64. 64.
    Asaka D, Yoshikawa M, Nakayama T, Yoshimura T, Moriyama H, Otori N. Elevated levels of interleukin-33 in the nasal secretions of patients with allergic rhinitis. Int Arch Allergy Immunol. 2012;158 Suppl 1:47–50.CrossRefPubMedGoogle Scholar
  65. 65.
    Baumann R, Rabaszowski M, Stenin I, Tilgner L, Gaertner-Akerboom M, Scheckenbach K, et al. Nasal levels of soluble IL-33R ST2 and IL-16 in allergic rhinitis: inverse correlation trends with disease severity. Clin Exp Allergy. 2013;43(10):1134–43.PubMedGoogle Scholar
  66. 66.
    Kamekura R, Kojima T, Takano K, Go M, Sawada N, Himi T. The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis. Clin Exp Allergy. 2012;42(2):218–28.CrossRefPubMedGoogle Scholar
  67. 67.
    Glück J, Rymarczyk B, Rogala B. Serum IL-33 but not ST2 level is elevated in intermittent allergic rhinitis and is a marker of the disease severity. Inflamm Res. 2012;61(6):547–50.PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.•
    Haenuki Y, Matsushita K, Futatsugi-Yumikura S, Ishii KJ, Kawagoe T, Imoto Y, et al. A critical role of IL-33 in experimental allergic rhinitis. J Allergy Clin Immunol. 2012;130(1):184–94. IL-33 required for manifestation of ragweed-induced allergic rhinitis in a mouse model; tissue expression of IL-33 protein reduced in the epithelium of allergic rhinitic patients compared to controls. CrossRefPubMedGoogle Scholar
  69. 69.
    Ishida A, Ohta N, Suzuki Y, Kakehata S, Okubo K, Ikeda H, et al. Expression of pendrin and periostin in allergic rhinitis and chronic rhinosinusitis. Allergol Int. 2012;61(4):589–95.CrossRefPubMedGoogle Scholar
  70. 70.
    Baumann R, Rabaszowski M, Stenin I, Gaertner-Akerboom M, Scheckenbach K, Wiltfang J, et al. The release of IL-31 and IL-13 after nasal allergen challenge and their relation to nasal symptoms. Clin Transl Allergy. 2012;2(1):13.PubMedCentralCrossRefPubMedGoogle Scholar
  71. 71.
    Shah SA, Ishinaga H, Hou B, Okano M, Takeuchi K. Effects of interleukin-31 on MUC5AC gene expression in nasal allergic inflammation. Pharmacology. 2013;91(3–4):158–64.CrossRefPubMedGoogle Scholar
  72. 72.
    Okano M, Fujiwara T, Higaki T, Makihara S, Haruna T, Noda Y, et al. Characterization of pollen antigen-induced IL-31 production by PBMCs in patients with allergic rhinitis. J Allergy Clin Immunol. 2011;127(1):277–9.CrossRefPubMedGoogle Scholar
  73. 73.
    Wang H, Liu Y, Liu Z. Clara cell 10-kD protein in inflammatory upper airway diseases. Curr Opin Allergy Clin Immunol. 2013;13(1):25–30.CrossRefPubMedGoogle Scholar
  74. 74.
    Benson M, Strannegård IL, Wennergren G, Strannegård O. Interleukin-5 and interleukin-8 in relation to eosinophils and neutrophils in nasal fluids from school children with seasonal allergic rhinitis. Pediatr Allergy Immunol. 1999;10(3):178–85.CrossRefPubMedGoogle Scholar
  75. 75.
    Pullerits T, Lindén A, Praks L, Cardell LO, Lötvall J. Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid. Clin Exp Allergy. 2000;30(10):1469–75.CrossRefPubMedGoogle Scholar
  76. 76.
    Benson M, Strannegård IL, Strannegård O, Wennergren G. Topical steroid treatment of allergic rhinitis decreases nasal fluid TH2 cytokines, eosinophils, eosinophil cationic protein, and IgE but has no significant effect on IFN-gamma, IL-1beta, TNF-alpha, or neutrophils. J Allergy Clin Immunol. 2000;106(2):307–12.CrossRefPubMedGoogle Scholar
  77. 77.
    Weido AJ, Reece LM, Alam R, Cook CK, Sim TC. Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis. Ann Allergy Asthma Immunol. 1996;77(5):407–15.CrossRefPubMedGoogle Scholar
  78. 78.
    Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341(7):468–75.CrossRefPubMedGoogle Scholar
  79. 79.
    Shamji MH, Ljørring C, Francis JN, Calderon MA, Larché M, Kimber I, et al. Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy. 2012;67(2):217–26.CrossRefPubMedGoogle Scholar
  80. 80.
    Wilson DR, Nouri-Aria KT, Walker SM, Pajno GB, O'Brien F, Jacobson MR, et al. Grass pollen immunotherapy: symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen season. J Allergy Clin Immunol. 2001;107(6):971–6.CrossRefPubMedGoogle Scholar
  81. 81.
    Klimek L, Dormann D, Jarman ER, Cromwell O, Riechelmann H, Reske-Kunz AB. Short-term preseasonal birch pollen allergoid immunotherapy influences symptoms, specific nasal provocation and cytokine levels in nasal secretions, but not peripheral T-cell responses, in patients with allergic rhinitis. Clin Exp Allergy. 1999;29(10):1326–35.CrossRefPubMedGoogle Scholar
  82. 82.
    Wachholz PA, Nouri-Aria KT, Wilson DR, Walker SM, Verhoef A, Till SJ, et al. Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios. Immunology. 2002;105(1):56–62.PubMedCentralCrossRefPubMedGoogle Scholar
  83. 83.
    Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK, et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol. 2004;172(5):3252–9.CrossRefPubMedGoogle Scholar
  84. 84.
    Secrist H, Chelen CJ, Wen Y, Marshall JD, Umetsu DT. Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med. 1993;178(6):2123–30.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Allergy and Clinical Immunology, Imperial College, LondonLondonUK

Personalised recommendations