Tear cytokine levels in allergic rhinitis without ocular symptoms (original) (raw)
Related papers
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2006
Background Several cytokines are involved in the recruitment and activation of inflammatory cells in ocular allergic diseases. The purpose of the study was to assay multiple cytokines and chemokines in tears, to compare subgroups of allergic conjunctivitis (AC) with controls, and in culture supernatants to determine whether conjunctival fibroblasts produce some of these cytokines. Methods Fifty to one hundred microlitre tears were obtained from patients with active seasonal allergic conjunctivitis (SAC; n = 12), vernal keratoconjunctivitis (VKC; n = 18), atopic keratoconjunctivitis (AKC; n = 6) and non-atopic controls (n = 14). Primary conjunctival fibroblasts grown in vitro were stimulated with IL-4, IL-13 or TNF-a for 24 h. Cell-free tear and culture supernatants were assayed for IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IFN-g, TNF-a, eotaxin, MCP-1 and RANTES using multiplex bead analysis. Induction of chemokine gene expression was determined by PCR. Results IL-1b, IL-2, IL-5, IL-6, IL-12, IL-13, MCP-1 were increased in all tears groups compared with controls, with highly significant correlations between many of these molecules. In addition IL-4, IFN-g, and IL-10 were elevated in SAC and VKC, while eotaxin and TNF-a were only increased in VKC. IL-6, IL-8, MCP-1, RANTES and eotaxin were detected from fibroblasts cultures, and were all up-regulated by TNF-a. By PCR, fibroblasts expressed MCP-1 transcripts constitutively, whereas IP-10 and Mig were up-regulated by TNF-a. Conclusions Differential cytokine levels support tears as a useful indicator of immune mechanisms occurring during AC. The striking similarities in chemokine profiles between tears and fibroblasts suggest these cells as likely sources of chemokines in tears.
2011
Nevertheless, there is a great dearth of data concerning both the clinical and the immunologic features of the secondary CR and the mechanism(s) through which the allergic reaction initiated in the nasal mucosa induces the secondary CR types. 1-3, 5-42 The purpose of this study was to investigate: (1) the appearance and possible concentration changes of some important mediators, such as histamine, tryptase, eosinophil cationic protein (ECP), leukotrienes, myeloperoxidase (MPO) and cytokines, such as, interferon-γ (IFN-γ), IL-2, IL-4 and IL-5 in tears during the secondary late CR; (2) the possible significance of these mediators in tears for the mechanism(s) underlying the secondary late CR. 2. Material and methods 2.1 Patients Thirty-one patients suffering from allergic conjunctivitis (SAC, n=13 and PAC, n=18) for more than 3 years, showing insufficient therapeutic compliance to the standard topical ophthalmologic treatment, having been referred to our
Tear Cytokine Levels in Vernal Keratoconjunctivitis
Cornea, 2013
The aims of this study were to evaluate the efficacy of topical 0.05% cyclosporine A on clinical signs and symptoms of vernal keratoconjunctivitis (VKC) and to examine its effect on tear cytokine levels. Methods: Twenty-one patients with active VKC and 15 healthy volunteers were included. Patients were treated with topical 0.05% cyclosporine A. Symptoms and signs were scored on the day of enrollment and at the end of month 1 and month 3. Tear and serum samples were collected before and on the third month of treatment. Interleukin (IL)-2, soluble IL-2 receptor (sIL-2R), IL-3, IL-4, IL-5, IL-6, IL-9, IL-13, IL-17, eotaxin, tumor necrosis factor alpha (TNF-a), and interferon gamma (IFN-g) in cell-free tear and serum supernatants were measured by multiplex bead analysis. Results: At the end of month 1 and month 3 with topical 0.05% cyclosporine A treatment, statistically a significant decrease was observed in sign and symptom scores of the patients (P , 0.0001). Tear IL-2, sIL-2R, IL-9, IL-17, IFN-g, and eotaxin levels in VKC patients were significantly higher than those in controls (P , 0.05). IL-3, IL-4, IL-5, and TNFa levels tended to be higher in VKC patients. There was also statistically significant reduction from before 0.05% cyclosporine A treatment to after treatment in tear levels of IL-4, IL-5, IL-17A, TNFa, IFN-g, and eotaxin (P , 0.05). IL-2 and sIL-2R levels tended to be lower than pretreatment levels. Conclusions: Topical 0.05% cyclosporine A is effective in alleviating signs and symptoms of VKC patients and shows its effect probably by decreasing the local production of some inflammatory mediators in tears.
Cellular changes in tears associated with keratoconjunctival responses induced by nasal allergy
Eye, 2014
Background Allergic keratoconjunctivitis occurs in a primary form, caused by an allergic reaction localized in the conjunctiva, and in a secondary form, induced by an allergic reaction originating in the nasal mucosa. Various hypersensitivity mechanisms involved in the keratoconjunctivitis forms result in different keratoconjunctival response types. Purpose To investigate the cytologic changes in tears during the secondary immediate (SIKCR), late (SLKCR), and delayed (SDYKCR) keratoconjunctival responses. Methods In 61 patients, comprising 20 SIKCRs, 23 SLKCRs, and 18 SDYKCRs, nasal provocation tests (NPTs) with allergens and 61 phosphate-buffered control challenges were repeated and supplemented with cell counting in the tears. Results The SIKCR (Po0.01), appearing 10-120 min after the NPT, was associated with increased eosinophil and mast cell counts in tears. The SLKCR (Po0.01), appearing 5-12 h after the NPT, was accompanied by increased counts of eosinophils, neutrophils, basophils, and conjunctival epithelial and goblet cells. The SDYKCR (Po0.05), appearing 24-48 h after NPT, was associated with increased counts of lymphocytes, neutrophils, monocytes, basophils, conjunctival epithelial, corneal epithelial and goblet cells. Conclusions The SIKCR, SLKCR, and SDYKCR, induced by nasal allergy, were associated with different cellular profiles in the tears. The cells, except mast, epithelial and goblet cells, displaying no intracellular changes, migrated probably from the conjunctival capillaries, in response to the factors released during the primary allergic reaction in the nasal mucosa and subsequently penetrating into the conjunctiva. These results demonstrate a causal role of nasal allergy and diagnostic value of NPT combined with recording of ocular features and cellular profiles in tears in some keratoconjunctivitis patients.
Allergic conjunctivitis and the impact of allergic rhinitis
Current allergy and asthma reports, 2010
Although nasal allergy has been prominent in allergy research, ocular allergy is increasingly recognized as a distinct symptom complex that imposes its own disease burden and reduction in patients' quality of life. In the past year, knowledge of the relationships between allergic conjunctivitis and allergic rhinitis has increased. Allergic conjunctivitis is highly prevalent and has a close epidemiologic relationship with allergic rhinitis. Both conditions also exhibit similar pathophysiologic mechanisms. Pathways of communication are thought to increase the likelihood of an inflammatory reaction at both sites following allergen exposure of nasal or ocular tissue. Clinical trials of intranasal therapies have demonstrated efficacy in allergic conjunctivitis and rhinitis. Newer intranasal steroids decrease ocular symptoms, potentially achieving efficacy by suppressing the naso-ocular reflex, downregulation of inflammatory cell expression, or restoration of nasolacrimal duct patency...
Molecular vision, 2013
The allergic reaction occurring primarily in the nasal mucosa can induce a secondary conjunctival response of an immediate (SICR), late (SLCR), or delayed (SDYCR) type in some patients with allergic conjunctivitis (AC). To investigate the concentration changes of histamine, tryptase, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), leukotrienes (LTB 4, LTC4, LTE4), myeloperoxidase (MPO), interferon-γ (IFN-γ), and interleukins (IL-2, IL-4, IL-5) in tears during the SICR, SLCR, and SDYCR. In 32 patients with AC, 11 SICR (p<0.01), 13 SLCR (p<0.001), and eight SDYCR (p<0.01) to nasal challenges with allergens (NPTs), the NPTs and 32 control tests with PBS were repeated and supplemented with the determination of these factors in tears. The SICRs were associated with significant concentration changes in tears (p<0.05) of histamine, tryptase, ECP, LTC4, and IL-4. The SLCRs were accompanied by significant changes in concentrations of histamine, ECP, LTB4, ...
Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients
PLoS ONE, 2011
Keratoconus, historically viewed as a non-inflammatory disease, is an ectatic corneal disorder associated with progressive thinning of the corneal stroma. Recently, a few inflammatory mediators have been reported to be elevated in the tear fluid of keratoconus patients. Consequently, we investigated a wide range of inflammation regulating cytokines in the tears and sera of keratoconus and control subjects. Interleukin (IL)-1b, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, interferon (IFN)-c, chemokine C-C motif ligand 5 (CCL5) and tumor necrosis factor (TNF)-a were tested in tear samples and sera of keratoconus and control individuals by multiplex immuno-bead assays. Selected cytokines were further tested by standard ELISA on pooled tear samples. All cytokines in the sera were generally low, with no significant changes between keratoconus and control subjects. However, in tear fluids, clear differences were detected between the two groups. These differences include increased IL-6, and decreased IL-12, TNF-a, IFN-c, IL-4, IL-13 and CCL5 in keratoconus compared to control tear fluids. The decreases in IL-12, TNF-a and CCL5 were statistically significant, while the IL-13 decrease was statistically significant in the severe keratoconus group only. IL-17 could not be detected by multiplex immuno-bead assay, but showed an increase in keratoconus by conventional ELISA on a limited number of pooled tear samples. Our findings confirm increased IL-6, but dispute earlier reports of increased TNF-a, and suggest a cytokine imbalance in keratoconus disrupting corneal homeostasis. Moreover, an increase in IL-17 suggests tissue degenerative processes at work, contributing to the thinning and weakening of the corneal connective tissue in keratoconus.
Tear and conjunctival changes during the allergen-induced early- and late-phase responses
Journal of Allergy and Clinical Immunology, 2000
Background: Allergic eye disease is common, but little is known about the underlying disease mechanisms. Conjunctival allergen challenge causes symptoms similar to those of seasonal allergic conjunctivitis and is a useful model to study. Objective: We have used allergen challenge to investigate the course of the ocular response, tear inflammatory mediators, tissue adhesion protein expression, and cellular infiltration. Methods: Eighteen atopic patients and 4 nonatopic control subjects were challenged with extracted mixed grass or Dermatophagoides pteronyssinus in one eye and control vehicle in the other. The clinical response was recorded, and tears were collected over a 6-hour period. Conjunctival biopsy specimens were taken from the challenged eye at 6 or 24 hours. Results: An early-phase response (maximal at 20 minutes) showed a significant increase in tear histamine and tryptase levels, reducing to control levels again by 40 minutes. At 6 hours, a late-phase response occurred with increased symptoms, a second peak of tear histamine and eosinophil cationic protein but not tryptase, upregulation of the adhesion molecules E-selectin and intercellular adhesion molecule, and a cellular infiltrate of mast cells, neutrophils, eosinophils, macrophages, and basophils, with T cells increased only in bulbar biopsy specimens. Conclusions: The early peaks of tear histamine plus tryptase indicate that the mast cell is responsible for the early-phase response, but basophils may be involved in the late-phase response. Both tear and biopsy findings underline the significance of the late-phase response as the transition between a type I response and clinical disease. (J Allergy Clin Immunol 2000;106:948-54.)