Advertisement

Tear cytokine levels in allergic rhinitis without ocular symptoms

Published:January 22, 2019DOI:https://doi.org/10.1016/j.jcjo.2018.12.003

      Abstract

      Objective

      To compare cytokine levels in the pre-corneal tear film between patients with allergic rhinitis, allergic rhinoconjunctivitis and the normal population.

      Design

      A comparative cross sectional study.

      Participants

      Patients were divided into Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal population).

      Methods

      A comparative cross-sectional study was conducted. Patients were divided into; Group 1 (allergic rhinitis without conjunctivitis), Group 2 (allergic rhinoconjunctivitis), and Group 3 (normal controls). Tears were collected using Schirmer strips and cytokine analysis performed using enzyme linked immunosorbent assay.

      Results

      There were a total of 68 subjects. Median values of cytokines in the allergic rhinitis group were as follows; TNFa (45.34 pg/ml), IL-4 (61.91 pg/ml), IL-5 (8.92 pg/ml), IL-6 (538.37 pg/ml) and IL-8 (1438.72 pg/ml). Cytokine levels in the group with allergic rhinoconjunctivitis were approximately two-fold higher than in the group with allergic rhinitis only. The median cytokine level in the control group was lowest. A significant inter-group difference was observed for TNF-alpha, IL-4, IL-6 and IL-8 levels, with allergic rhinoconjunctivitis patients demonstrating significantly elevated cytokines compared to those with allergic rhinitis only (p<0.001). These four cytokines were also significantly higher in those with allergic rhinitis than in controls (p<0.005). Although the group with allergic rhinoconjunctivitis had the highest levels of IL-5, no statistically significant inter-group difference was noted (p=0.479).

      Conclusion

      This study demonstrated the presence of raised tear film inflammatory cytokines even in allergic rhinitis patients without ocular symptoms. These patients may be at increased risk of developing allergic conjunctivitis. These findings not only substantiate the immunological theory of the naso-ocular reflex, but have clinical and therapeutic implications for the holistic management of allergic rhinitis and conjunctivitis.

      Résumé

      Objectif

      Comparer le taux de cytokines du film lacrymal précornéen chez le sujet présentant une rhinite allergique, chez le sujet souffrant de rhinoconjonctivite allergique et chez le sujet sain.

      Nature

      Étude transversale comparative.

      Participants

      Les 68 sujets ont été répartis en 3 groupes: rhinite allergique sans conjonctivite, rhinoconjonctivite allergique et population saine.

      Méthodes

      On a procédé à une étude transversale comparative au cours de laquelle les patients ont été répartis en 3 groupes: groupe 1 (rhinite allergique sans conjonctivite), groupe 2 (rhinoconjonctivite allergique) et groupe 3 (sujets témoins). On a recueilli des larmes au moyen d'un ruban de papier filtre afin de réaliser un test de Schirmer. L'analyse des cytokines a été réalisée par essai immuno-enzymatique ELISA (enzyme linked immunosorbent assay).

      Résultats

      Chez l'ensemble des 68 sujets, le taux médian de cytokines dans le groupe rhinite allergique se chiffrait comme suit: TNF-α (45,34 pg/mL), IL-4 (61,91 pg/mL), IL-5 (8,92 pg/mL), IL-6 (538,37 pg/mL) et IL-8 (1438,72 pg/mL). Le taux de cytokines dans le groupe rhinoconjonctivite allergique était approximativement 2 fois plus élevé que le taux enregistré dans le groupe rhinite allergique seule. Le taux médian de cytokines était le moins élevé dans le groupe témoin. On a noté une différence inter-groupe significative quant au taux de TNF-α, d'IL-4, d'IL-6 et d'IL-8; le taux de cytokines était significativement plus élevé chez les patients du groupe rhinoconjonctivite allergique comparativement à ceux du groupe rhinite allergique seule (p < 0,001). Le taux de ces 4 cytokines était en outre significativement plus élevé chez les sujets qui souffraient de rhinite allergique comparativement aux sujets témoins (p < 0,005). Bien que le taux d'IL-5 ait été le plus élevé dans le groupe rhinoconjonctivite allergique, on ne note aucune différence inter-groupe statistiquement significative à ce chapitre (p = 0,479).

      Conclusion

      Cette étude met au jour une hausse du taux des cytokines inflammatoires dans le film lacrymal même chez les patients souffrant de rhinite allergique sans symptômes oculaires. Ces sujets sont peut-être exposés à un risque plus élevé de conjonctivite allergique. Nos résultats étayent la théorie immunologique du réflexe naso-oculaire, sans compter qu'ils font ressortir les répercussions cliniques et thérapeutiques de la prise en charge globale de la rhinite et de la conjonctivite allergique.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Canadian Journal of Ophthalmology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Perkin MR
        • Bader T
        • Rudnicka AR
        • Strachan DP
        • Owen CG
        Inter-relationship between rhinitis and conjunctivitis in allergic rhinoconjunctivitis and associated risk factors in rural UK children.
        PLoS One. 2015; 10e0143651
        • Katelaris CH
        • Sacks R
        • Theron PN
        Allergic rhinoconjunctivitis in the Australian population: burden of disease and attitudes to intranasal corticosteroid treatment.
        Am J Rhinol Allergy. 2013; 27: 506-509
        • Scadding G
        Cytokine profiles in allergic rhinitis.
        Curr Allergy Asthma Rep. 2014; 14: 435
        • Yuksel Elgin C
        • Iskeleli G
        • Talaz S
        • Akyol S
        Comparative analysis of tear film levels of inflammatory mediators in contact lens users.
        Curr Eye Res. 2016; 41: 441-447
        • Sorkhabi R
        • Ghorbanihaghjo A
        • Taheri N
        • Ahoor MH
        Tear film inflammatory mediators in patients with keratoconus.
        Int Ophthalmol. 2015; 35: 467-472
        • Lee JH
        • Min K
        • Kim SK
        • Kim EK
        • Kim TI
        Inflammatory cytokine and osmolarity changes in the tears of dry eye patients treated with topical 1% methylprednisolone.
        Yonsei Med J. 2014; 55: 203-208
        • Huang D
        • Xu N
        • Song Y
        • Wang P
        • Yang H
        Inflammatory cytokine profiles in the tears of thyroid-associated ophthalmopathy.
        Graefes Arch Clin Exp Ophthalmol. 2012; 250: 619-625
        • Bousquet J
        • Van Cauwenberge P
        • Khaltaev N
        • Aria Workshop Group
        • World Health Organization
        Allergic rhinitis and its impact on asthma.
        J Allergy Clin Immunol. 2001; 108: S147-S334
        • Buckley RJ
        Vernal keratoconjunctivitis.
        Int Ophthalmol Clin. 1988; 28: 303-308
        • Rathi VM
        • Murthy SI
        Allergic conjunctivitis.
        Community Eye Health. 2017; 30: S7-10
        • Greiner AN
        • Hellings PW
        • Rotiroti G
        • Scadding GK
        Allergic rhinitis.
        Lancet. 2011; 378: 2112-2122
        • Hom MM
        • Bielory L
        The anatomical and functional relationship between allergic conjunctivitis and allergic rhinitis.
        Allergy Rhinol (Providence). 2013; 4: e110-e119
        • Callebaut I
        • De Vries A
        • Steelant B
        • et al.
        Nasal allergen deposition leads to conjunctival mast cell degranulation in allergic rhinoconjunctivitis.
        Am J Rhinol Allergy. 2014; 28: 290-296
        • Callebaut I
        • Spielberg L
        • Hox V
        • et al.
        Conjunctival effects of a selective nasal pollen provocation.
        Allergy. 2010; 65: 1173-1181
        • Hafez SF
        • Sallam MM
        • Ibraheem SA
        Local expression of IL-4 and IL-5 in perennial allergic rhinitis and their modulation by topical corticosteroid therapy.
        Egypt J Immunol. 2004; 11: 111-121
        • Zhao J
        • Wang S
        • Ma F
        Changes of Th1, Th2 cells and correlative cytokines in allergic rhinitis [in Chinese].
        Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2005; 19: 794-796
        • Wynn TA
        Type 2 cytokines: mechanisms and therapeutic strategies.
        Nat Rev Immunol. 2015; 15: 271-282
        • Leonardi A
        • Fregona IA
        • Plebani M
        • Secchi AG
        • Calder VL
        Th1- and Th2-type cytokines in chronic ocular allergy.
        Graefes Arch Clin Exp Ophthalmol. 2006; 244: 1240-1245
        • Li ZP
        • Yin LL
        • Wang H
        • Liu LS
        Association between promoter polymorphisms of interleukin-4 gene and allergic rhinitis risk: a meta-analysis.
        J Huazhong Univ Sci Technolog Med Sci. 2014; 34: 306-313
        • Gluck J
        • Rogala B
        • Rogala E
        • Oleś E
        Allergen immunotherapy in intermittent allergic rhinitis reduces the intracellular expression of IL-4 by CD8+ T cells.
        Vaccine. 2007; 26: 77-81
        • Scadding GW
        • Eifan AO
        • Lao-Araya M
        • et al.
        Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge.
        Allergy. 2015; 70: 689-696
        • Bradding P
        • Feather IH
        • Wilson S
        • et al.
        Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation.
        J Immunol. 1993; 151: 3853-3865
        • Tsai YJ
        • Hao SP
        • Chen CL
        • Wu WB
        Thromboxane A2 regulates CXCL1 and CXCL8 chemokine expression in the nasal mucosa-derived fibroblasts of chronic rhinosinusitis patients.
        PLoS One. 2016; 11e0158438
        • Wang Z
        The effect of TNF-alpha & IL-8 in the pathogenesis of allergic rhinitis [in Chinese].
        Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2006; 20: 1060-1061
        • Leonardi A
        • Curnow SJ
        • Zhan H
        • Calder VL
        Multiple cytokines in human tear specimens in seasonal and chronic allergic eye disease and in conjunctival fibroblast cultures.
        Clin Exp Allergy. 2006; 36: 777-784
        • Macleod JD
        • Anderson DF
        • Baddeley SM
        • Holgate ST
        • McGill JI
        • Roche WR
        Immunolocalization of cytokines to mast cells in normal and allergic conjunctiva.
        Clin Exp Allergy. 1997; 27: 1328-1334
        • Nakai Y
        • Ohashi Y
        • Kakinoki Y
        • et al.
        Allergen-induced mRNA expression of IL-5, but not of IL-4 and IFN-gamma, in peripheral blood mononuclear cells is a key feature of clinical manifestation of seasonal allergic rhinitis.
        Arch Otolaryngol Head Neck Surg. 2000; 126: 992-996
        • Comert S
        • Karakaya G
        • Kalyoncu AF
        Wraparound eyeglasses improve symptoms and quality of life in patients with seasonal allergic rhinoconjunctivitis.
        Int Forum Allergy Rhinol. 2016; 6: 722-730
        • Lightman S
        • Scadding GK
        Should intranasal corticosteroids be used for the treatment of ocular symptoms of allergic rhinoconjunctivitis? A review of their efficacy and safety profile.
        Int Arch Allergy Immunol. 2012; 158: 317-325
        • Igarashi T
        • Nakazato Y
        • Kunishige T
        • et al.
        Mometasone furoate nasal spray relieves the ocular symptoms of seasonal allergic rhinoconjunctivitis.
        J Nippon Med Sch. 2012; 79: 182-189
        • D'Amato G
        • D'Amato M
        • Rumi G
        • Cantera E
        • Cortes M
        • Dattilo R
        Improvement of quality of life in allergic rhinoconjunctivitis patients using nasal filters, a preliminary study.
        Eur Ann Allergy Clin Immunol. 2013; 45: 167-175
        • Aneeza WH
        • Husain S
        • Rahman RA
        • Van Dort D
        • Abdullah A
        • Gendeh BS
        Efficacy of mometasone furoate and fluticasone furoate on persistent allergic rhinoconjunctivitis.
        Allergy Rhinol (Providence). 2013; 4: e120-e126
        • Callebaut I
        • Vandewalle E
        • Hox V
        • et al.
        Nasal corticosteroid treatment reduces substance P levels in tear fluid in allergic rhinoconjunctivitis.
        Ann Allergy Asthma Immunol. 2012; 109: 141-146
        • Carr WW
        • Ratner P
        • Munzel U
        • et al.
        Comparison of intranasal azelastine to intranasal fluticasone propionate for symptom control in moderate-to-severe seasonal allergic rhinitis.
        Allergy Asthma Proc. 2012; 33: 450-458
        • Brehler R
        • Stocker B
        • Grundmann S
        Allergy–current insights into prevention and diagnostic workup of immediate-type allergy and treatment of allergic rhinoconjunctivitis.
        J Dtsch Dermatol Ges. 2015; 13 (quiz 763–4): 747-762
        • Abelson MB
        • Turner D
        A randomized, double-blind, parallel-group comparison of olopatadine 0.1% ophthalmic solution versus placebo for controlling the signs and symptoms of seasonal allergic conjunctivitis and rhinoconjunctivitis.
        Clin Ther. 2003; 25: 931-947
        • Spangler DL
        • Abelson MB
        • Ober A
        • Gotnes PJ
        Randomized, double-masked comparison of olopatadine ophthalmic solution, mometasone furoate monohydrate nasal spray, and fexofenadine hydrochloride tablets using the conjunctival and nasal allergen challenge models.
        Clin Ther. 2003; 25: 2245-2267