Abstract
Background
Previous reports have suggested that Th2-type cytokines are important in the pathogenesis of ocular allergic diseases. The purpose of this study is to measure levels and mRNA expression of Th1- and Th2-type cytokines in patients with active vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).
Methods
Tear samples and tear-isolated cells were obtained from 9 healthy participants (CT—controls), 28 VKC, and 6 AKC patients. IL-4, IL-13, and interferon gamma (IFNγ) tear levels were determined by ELISA, and IL-4 and IFNγ tear cell mRNA expression by RT-PCR. Effects of these cytokines on IL-6 and IL-8 secretion, and on ICAM-1 expression by conjunctival fibroblasts, were evaluated by ELISA and flow cytometry respectively.
Results
Interleukin-4 tear levels were increased in VKC and AKC compared with CT, but only IFNγ significantly correlated with corneal involvement. An IL-4/13-dominant profile was found in 50% of VKC and in 17% of AKC patients, while a IFNγ -dominant profile was found in 18% of VKC and in 17% of AKC patients. IL-4 and IFNγ transcripts were detected in tear cells from 11 out of 12 VKC patients. IFNγ upregulated expression of ICAM-1 on conjunctival fibroblasts and the secretion of IL-6 and IL-8.
Conclusions
Although both IL-4 and IFNγ are detected in tears, only IFNγ levels correlated with disease severity and upregulated ICAM-1 on conjunctival fibroblasts, suggesting the role of IFNγ in the inflammatory phase of chronic allergic eye diseases.
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References
Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793
Abu El-Asrar AM, Struyf S, Al-Kharashi SA, Missotten L, Van Damme J, Geboes K (2000) Chemokines in the limbal form of vernal keratoconjunctivitis. Br J Ophthalmol 84:1360–1366
Abu El-Asrar AM, Struyf S, Al-Kharashi SA, Missotten L, Van Damme J, Geboes K (2003) The T-lymphocyte chemoattractant Mig is highly expressed in vernal keratoconjunctivitis. Am J Ophthalmol 136:853–860
Calder VL, Jolly G, Hingorani M, Adamson P, Leonardi A, Secchi AG, Buckley R, Lightman S (1999) Cytokine production and mRNA expression by conjunctival T cell lines in chronic allergic eye diseases. Clin Exp Allergy 29:1214–1222
Coffman RL, Seymour BW, Lebman DA, Hiraki DD, Christiansen JA, Shrader B, Cherwinski HM, Savelkoul HF, Finkelman FD, Bond MW (1988) The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev 102:5–28
Fujitsu Y, Fukuda K, Kimura K, Seki K, Kumagai N, Nishida T (2005) Protection of human conjunctival fibroblasts from NO-induced apoptosis by interleukin-4 or interleukin-13. Invest Ophthalmol Vis Sc 46:797–802
Fukushima A, Fukata K, Ozaki A, Takata M, Kuroda N, Enzan H, Ueno H (2002) Exertion of the suppressive effects of IFN-gamma on experimental immune mediated blepharoconjunctivitis in Brown Norway rats during the induction phase but not the effector phase. Br J Ophthalmol 86:1166–1171
Hansen G, Berry G, DeKruyff RH, Umetsu DT (1999) Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J Clin Invest 103:175–183
Larche’ M, Robinson DS, Kay AB (2003) The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol 111:450–463
Leonardi A, DeFranchis G, Zancanaro F, Crivellari G, DePaoli M, Plebani M, Secchi AG (1999) Identification of local Th2 and Th0 lymphocytes in vernal conjunctivitis by cytokine flow cytometry. Invest Ophthalmol Vis Sci 40:3036–3040
Leonardi A, Radice M, Fregona IA, Plebani M, Abatangelo G, Secchi AG (1999) Histamine effects on conjunctival fibroblasts from patients with vernal conjunctivitis. Exp Eye Res 68:739–746
Leonardi A, Borghesan F, DePaoli M, Plebani M, Secchi AG (2000) Tear and serum soluble leukocyte activation markers in conjunctival allergic diseases. Am J Ophthalmol 129:151–158
Leonardi A, DeFranchis G, DePaoli M, Fregona IA, Plebani M, Secchi AG (2002) Histamine-induced cytokine production and ICAM-1 expression in human conjunctival fibroblasts. Curr Eye Res 25:189–196
Leonardi A, Jose PJ, Zhan H, Calder VL (2003) Tear and mucus eotaxin-1 and eotaxin-2 in allergic keratoconjunctivitis. Ophthalmology 110:487–492
Leonardi A, Cortivo R, Fregona IA, Plebani M, Secchi AG, Abatangelo G (2003) The effects of Th2 cytokines on collagen, MMP-1 and TIMP-1 expression in conjunctival fibroblasts. Invest Ophthalmol Vis Sci 44:183–189
Maggi E, Biswas P, Del Prete G, Parronchi P, Macchia D, Simonelli C, Emmi L, De Carli M, Tiri A, Ricci M, Romagnani S (1991) Accumulation of Th-2-like helper T cells in the conjunctiva of patients with vernal conjunctivitis. J Immunol 146:1169–1174
Magone MT, Whitcup SM, Fukushima A, Chan CC, Silver PB, Rizzo LV (2000) The role of IL-12 in the induction of late-phase cellular infiltration in a murine model of allergic conjunctivitis. J Allergy Clin Immunol 105:299–308
Matsura N, Uchio E, Nakazawa M, Yago T, Matsumoto S, Ohno S, Minami M (2004) Predominance of infiltrating IL-4-producing T cells in conjunctiva of patients with allergic conjunctival disease. Curr Eye Res 29:235–243
Metz DP, Bacon AS, Holgate S, Lightman SL (1996) Phenotypic characterization of T cells infiltrating the conjunctiva in chronic allergic eye disease. J Allergy Clin Immunol 98:686–696
Metz DP, Hingorani M, Calder VL, Buckley RJ, Lightman SL (1997) T-cell cytokines in chronic allergic eye disease. J Allergy Clin Immunol 100:817–824
Montan PG, Scheynius A, van der Ploeg I (2002) Similar T helper Th2-like cytokine mRNA expression in vernal keratoconjunctivitis regardless of atopic constitution. Allergy 57:436–441
Nivenius E, Montan PG, Chryssanthou E, Jung K, van Hage-Hamsten M, van der Ploeg I (2004) No apparent association between periocular and ocular microcolonization and the degree of inflammation in patients with atopic keratoconjunctivitis. Clin Exp Allergy 34:725–730
Stahl JL, Cook EB, Graziano FM, Barney NP (2003) Differential and cooperative effects of TNF alpha, IL-1 beta, and IFN gamma on human cell conjunctival epithelial cell receptor expression and chemokine release. Invest Ophthalmol Visual Sci 44:2010–2015
Stern ME, Siemasko K, Gao J, Duong A, Beauregard C, Calder V, Niederkorn JY (2005) Role of Interferon-gamma in a mouse model of allergic conjunctivitis. Invest Ophthalmol Vis Sci 46:3239–3246
Trocme SD, Aldave AJ (1994) The eye and the eosinophil. Surv Ophthalmol 39:241–252
Trocme SD, Hallberg CK, Gill KS, Gleich GJ, Tyring SK, Brysk MM (1997) Effects of eosinophil granule proteins on human corneal epithelial cell viability and morphology. Invest Ophthalmol Vis Sci 38:593–599
Uchio E, Ono SY, Ikezawa Z, Ohno S (2000) Tear levels of interferon-gamma, interleukin (IL) -2, IL-4 and IL-5 in patients with vernal keratoconjunctivitis, atopic keratoconjunctivitis and allergic conjunctivitis. Clin Exp Allergy 30:103–109
Yannariello-Brown J, Hallberg CK, Haberle H, Brysk MM, Jiang Z, Patel JA, Ernst PB, Trocme SD (1998) Cytokine modulation of human corneal epithelial cell ICAM-1 (CD54) expression. Exp Eye Res 67:383–393
Zhan H, Towler HM, Calder VL (2003) The immunomodulatory role of human conjunctival epithelial cells. Invest Ophthalmol Vis Sci 44:3906–3910
Acknowledgements
Grant support: in part by The Royal Society European Science Exchange Program (ESEP) (VC, AL); Trustees of Fight For Sight UK (VC). Commercial relationship: none.
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Leonardi, A., Fregona, I.A., Plebani, M. et al. Th1- and Th2-type cytokines in chronic ocular allergy. Graefe's Arch Clin Exp Ophthalmo 244, 1240–1245 (2006). https://doi.org/10.1007/s00417-006-0285-7
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DOI: https://doi.org/10.1007/s00417-006-0285-7