Conjunctival Eosinophil Research Articles

JACQLQ subjective symptom questionnaire score and clinical test results for patients with allergic conjunctival disease

We investigated the relationship between subjective symptoms and objective findings in patients with allergic conjunctival diseases (ACD) and test results for tear total IgE (t-tIgE), conjunctival eosinophils (c-Eo), serum total IgE (s-tIgE), serum-antigen specific IgE (s-sIgE), and serum eosinophils (s-Eo). Subjective symptoms and objective findings of patients with ACD were evaluated using Japanese Allergic Conjunctival Disease Quality of Life Questionnaire (JACQLQ), which described disability score and emotional score written by patient and clinical findings score written by ophthalmologist. We investigated the relationship between questionnaire scores and laboratory data for t-tIgE, c-Eo, s-tIgE, s-sIgE, and s-Eo. Scores of impediments to life and of moods were highest in vernal keratoconjunctivitis among ACD. Cases with positive pollen-sIgE showed significantly more nasal symptom score than those with negative pollen-sIgE (P < 0.05). Cases with positive t-tIgE or c-Eo showed significantly more objective symptoms’ JACQLQ score than those with negative t-tIgE or c-Eo (P < 0.05), respectively. Cases positive for house dust/mite-sIgE, showed significantly more objective symptoms’ JACQLQ score than those without for house dust/mite-sIgE (P < 0.05). These results indicate that ACD could be analyzed more accurately by the combination of JACQLQ and laboratory data.

Prophylactic and Therapeutic Effects of Oral Immunotherapy on Birch Pollen-Induced Allergic Conjunctivitis in Mice with a Rice-Based Edible Vaccine Expressing a Hypoallergenic Birch Pollen Allergen.

We investigated the prophylactic and therapeutic effects of the oral administration of transgenic rice seeds expressing a hypoallergenic Bet v 1 derivative of allergic birch pollen conjunctivitis in mice. Transgenic rice seed depositing a chimeric molecule called TPC7 (tree pollen chimera 7) created by DNA shuffling of Bet v 1 family sequences from birch, alder and hazel in protein bodies of endosperm was generated. BALB/c mice were sensitized to birch pollen in alum and challenged with pollen in eyedrops. They were fed TPC7 transgenic or non-transgenic (control) rice seeds for 14 d before sensitization (prophylactic protocol) or 17 d after sensitization (therapeutic protocol). The clinical score and number of conjunctival eosinophils were significantly lower in TPC7-fed mice than in the control mice based on both the prophylactic and therapeutic protocols. Serum concentration of allergen-specific IgE did not differ between TPC7-fed and control groups in either protocol. Prophylactic administration of TPC7 downregulated the production of IL-4 and IFN-γ, whereas therapeutic administration of TPC7 upregulated the production of IFN-γ by allergen-stimulated splenocytes. Prophylactic or therapeutic oral administration of transgenic rice expressing TPC7 suppressed birch pollen-induced allergic conjunctivitis in mice. Feeding transgenic rice is a potentially effective approach as an allergen-specific immunotherapy for allergic conjunctivitis.

Meibomian gland dysfunction is suppressed via selective inhibition of immune responses by topical LFA-1/ICAM antagonism with lifitegrast in the allergic eye disease (AED) model

PurposeThe etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meibum) to the tear film and is a major cause of dry eye. Work in the allergic eye disease (AED) mouse model has revealed an immunopathogenic role in MGD causation, now raising interest in the applicability of immunomodulatory therapies. As such, we herein ask whether inhibition of lymphocyte function associated antigen (LFA)-1/intracellular adhesion molecules (ICAM)-1 signaling via topical lifitegrast administration has a therapeutic effect on MGD in AED mice. MethodsMice were induced with AED by i.p. injection of ovalbumin (OVA) mixed with alum and pertussis toxin, followed 2 weeks later by once daily topical OVA challenges for 7 days. Mice were treated topically with 5% lifitegrast ophthalmic solution or vehicle (PBS) 30 min prior to challenge. We developed a clinical ranking method to assess MGD severity, and also scored clinical allergy. Conjunctivae and draining lymph nodes were collected for flow cytometry. ResultsTopical lifitegrast significantly inhibited clinical MGD severity, which was associated with diminished pathogenic TH17 cell and neutrophil numbers in the conjunctiva. No significant change in conjunctival TH2 cells or eosinophils, and only marginal differences in ocular allergy were observed. ConclusionsIn AED mice, lifitegrast inhibited MGD severity marked by a reduction in select immune populations in the conjunctiva. Our findings warrant future examination of lifitegrast in the treatment of patients with forms of MGD.

Sympathetic Nerves Positively Regulate Eosinophil-Driven Allergic Conjunctivitis via α1-Adrenergic Receptor Signaling

Eosinophils are a major cause of tissue injury in allergic conjunctivitis. The biological nature of eosinophils in the conjunctiva and the mechanisms that control eosinophils' responses in allergic conjunctivitis are currently not completely understood. This study reports that conjunctival eosinophils comprise two populations-Siglec-Fint and Siglec-Fhi-in different life stages. Siglec-Fint eosinophils partly expressed CD34 and were in the immature (or steady) state. Siglec-Fhi eosinophils did not express CD34, sharply increased in number after short ragweed (SRW) pollen challenge, and were in the mature (or activated) state. Moreover, chemical sympathectomy by 6-hydroxydopamine reduced the recruitment and activation of eosinophils, whereas the activation of the sympathetic nerve system (SNS) with restraint stress accelerated the recruitment and activation of eosinophils in SRW-induced conjunctivitis. It was also found that two eosinophil populations expressed alpha-1a-adrenergic receptors (α1a-ARs); in SRW-induced conjunctivitis, treatment with an α1a-AR antagonist decreased eosinophil responses, whereas treatment with an α1a-AR agonist aggravated eosinophil responses. Thus, eosinophil responses in conjunctivitis are regulated by the SNS via α1a-AR signaling. SNS inputs or α1a-AR function may be potential targets for the treatment of allergic conjunctivitis.

D451 CLINICAL ACTIVITY OF AK002, AN ANTI-SIGLEC-8 ANTIBODY, IN SEVERE ALLERGIC CONJUNCTIVITIS AND COMORBID ATOPIC DISEASES

Severe allergic conjunctivitis (AC) can lead to debilitating ocular symptoms with a risk of vision loss. Driven primarily by conjunctival mast cells and eosinophils, AC is also commonly associated with atopic conditions such as atopic dermatitis, asthma, and rhinitis. AC can present in various forms including atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), and perennial allergic conjunctivitis (PAC). AK002 is an anti-Siglec-8 antibody that selectively depletes eosinophils and inhibits mast cells. This open-label study is the first evaluation of the safety, tolerability, and efficacy of AK002 in AC.

Topical Administration of β-1,3-Glucan to Modulate Allergic Conjunctivitis in a Murine Model.

Recent studies on β-1,3-glucan (BG), a cell wall component of a variety of fungi, yeasts, and bacteria, demonstrated that it affects the balance of Th1/Th2 immune responses. We therefore determined whether topical application of BG modulates ocular allergy in a murine model. We sensitized 7- to 8-week-old BALB/c mice once with ovalbumin (OVA) and aluminum hydroxide via intraperitoneal injection. Mice were rested for 2 weeks and then challenged by instillation of OVA eye drops once daily for 13 days. We administered BG eye drops 5 minutes after OVA challenge once daily. Clinical signs were measured, the infiltration of eosinophils and mast cells into conjunctiva was assessed with flow cytometry, and the serum levels of OVA-specific IgE production and Th2 cytokines after in vitro stimulation of T cells in draining lymph nodes (LN) were determined. Mice treated with BG showed attenuated allergic conjunctivitis, as indicated by clinical signs and decreased production of serum OVA-specific IgE. In addition, BG treatment led to decreased infiltration of CD45+ immune cells, eosinophils, and mast cells into the conjunctiva, compared with the mice treated with vehicle alone (control mice). Administration of BG suppressed Th2 cytokine production in in vitro T-cell assays partially through the induction of interleukin (IL)-10-producing CD4 T cells in draining LNs. Taken together, these results suggest that BG is capable of stimulating IL-10-producing CD4+ T cells and suppressing both the Th2 response in draining LNs and conjunctival eosinophil infiltration. We therefore demonstrated the therapeutic potential of topical BG administration for allergic conjunctivitis.

A Clinical Study of Vernal Keratoconjunctivitis

Objectives: To study the variations in epidemiological characteristics, clinical features, disease process and various modalities of management in VKC. Materials and Methods: A hospital based prospective study of 70 patients presenting with symptoms of allergic conjunctivitis was done at Department of Ophthalmology, J.J.M. Medical College, Davangere, from June 2012 to May 2013. Multiple epidemiological (age, sex) and clinical parameters (type, symptoms, treatment, failure of treatment) were studied. All patients were appropriately managed and reviewed once in fortnight and follow up ranged from a minimum of 3 months to 6 months.Results: Vernal keratoconjunctivitis was found to be the commonest type (64.3%) of allergic conjunctivitis. It was found to affect young males below 16 years (66.7%). Mean age group to be affected was 13.75 years with a mean duration of 4.87 years. Seasonal occurrence (75.5%) and itching (100%) were the predominant features. Palpebral form was the most common form of the disease (49%). Pulse steroid therapy was found to be a safe and effective method of management of vernal conjunctivitis. Conclusion: VKC is a common form of allergic conjunctivitis in a tropical country like ours. It is a bilateral, recurrent debilitating form of disease found to affect young males below 16 years. VKC is associated with other systemic atopy or family history of allergic disorders. Conjunctival eosinophils can be used as an evidence for diagnosis of VKC.

Rebamipide Suppresses PolyI:C-Stimulated Cytokine Production in Human Conjunctival Epithelial Cells

We previously documented that ocular surface epithelial cells could regulate ocular surface inflammation and suggested that, while Toll-like receptor 3 upregulates, EP3, one of the prostaglandin E2 receptors, downregulates ocular surface inflammation. Others reported that rebamipide, a gastroprotective drug, could not only increase the gastric mucus production, but also suppressed gastric mucosal inflammation and that it was dominantly distributed in mucosal tissues. The eyedrop form of rebamipide, approved in Japan for use in the treatment of dry eye diseases, upregulates mucin secretion and production, thereby suppressing superficial punctate keratopathy on the ocular surface of patients with this disease. In the current study, we investigated whether rebamipide has anti- inflammatory effects on the ocular surface. To examine the effects of rebamipide on polyI:C-induced cytokine expression by primary human conjunctival epithelial cells, we used enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction assay. We studied the effects of rebamipide on ocular surface inflammation in our murine experimental allergic conjunctivitis (EAC) model. Rebamipide could suppress polyI:C-induced cytokine production and the expression of mRNAs for CXCL10, CXCL11, RANTES, MCP-1, and IL-6 in human conjunctival epithelial cells. In our EAC model, the topical administration of rebamipide suppressed conjunctival allergic eosinophil infiltration. The topical application of rebamipide on the ocular surface might suppress ocular surface inflammation by suppressing the production of cytokines by ocular surface epithelial cells.

Topical tacrolimus for the management of acute allergic conjunctivitis in a mouse model

Acute allergic conjunctivitis is a constantly challenging condition that often requires steroids for effective management. Alternative treatment options are needed due to the potential side effects of steroids. Tacrolimus has been used for vernal/atopic conjunctivitis. The aim of our study was to investigate the therapeutic effect of topical administration of 0.03% tacrolimus (eye drops or ointment) in comparison to 0.1% dexamethasone in a mouse model of acute allergic conjunctivitis. BALB/c mice were sensitized by an intraperitoneal injection of 10μg/0.2ml ovalbumin (OVA) absorbed on ALUM (2.0mg) on days 1 and 8. They were challenged by topical instillation of 2μl of 15% OVA (absorbed in 10% glycerol) twice daily, on days 15-21. Treatment was administered twice daily on days 17-21. Mice were randomly assigned topical treatment groups: Group 1, 0.1% dexamethasone drops; Group 2, 0.03% tacrolimus drops; Group 3, 0.03% tacrolimus ointment; Group 4 PBS drops (control). On day 22 all mice underwent clinical evaluation, blood sampling for IgE levels, and conjunctivas were removed for eosinophil counting. IgE and OVA-specific IgE levels were similar among all groups, demonstrating induction of allergic reaction in all mice. Significantly lower clinical scores were found among all treated groups as compared to controls (P < 0.001), while no significant difference was found among the three treatment groups (P > 0.05). Conjunctival eosinophil counts were significantly lower in Group 1 (P < 0.05) as compared to the other groups. The clinical efficacy of topical 0.03% tacrolimus was similar to 0.1% dexamethasone for acute allergic conjunctivitis.

B and T lymphocyte attenuator regulates the development of antigen-induced experimental conjunctivitis

To investigate the roles that B and T lymphocyte attenuator (BTLA) and herpesvirus entry mediator (HVEM) play in the development of antigen-induced experimental conjunctivitis (EC). BALB/c mice were immunized with ragweed (RW) in alum. Ten days later, the mice were challenged with RW in eye drops. After 24hours, the conjunctivas, blood and spleens were collected for histological analysis, measurement of serum immunoglobulin (Ig) levels, and both flow cytometric analysis and cytokine assays, respectively. The mice were injected intraperitoneally with anti-BTLA antibody, anti-HVEM antibody or control antibody during either induction phase or effector phase. Induction-phase treatment with anti-BTLA antibody but not anti-HVEM antibody significantly increased conjunctival eosinophil infiltration. Treatment with either antibody during the effector phase did not affect conjunctival eosinophil infiltration. Anti-BTLA antibody treatment during the induction phase reduced the B cell compartment and increased the CD11b-positive cell compartment in splenocytes. Additionally, anti-BTLA treatment upregulated IL-4 and IL-10 production of splenocytes stimulated by RW. BTLA regulated the development of EC possibly by downregulating Th2 cytokine production and adjusting the compartments of immunocompetent cells. The regulation of EC by BTLA may be mediated by BTLA ligands other than HVEM.

Comparison of effects of alcaftadine and olopatadine on conjunctival epithelium and eosinophil recruitment in a murine model of allergic conjunctivitis

Background:Antihistamines constitute the first line of therapy for allergic conjunctivitis, and are safe and effective in relieving the signs and symptoms of ocular allergy. Despite this, they are less effective than some other drugs in relieving delayed symptoms of allergic conjunctivitis. Recent evidence suggests that changes in the conjunctival epithelium may underlie aspects of delayed reactions. In this study we compared two antihistamines, olopatadine and alcaftadine, for their ability to modify epithelial cell changes associated with allergic conjunctivitis at time points selected to reflect late-phase reactions.Methods:Studies employed a modified conjunctival allergen challenge model. Sensitized mice were challenged with topical allergen with or without drug treatments. Treatment groups were assayed for acute-phase (15 minutes) and delayed-phase (24 hours) responses. Groups were scored for allergy symptoms (redness, itch, tearing, and edema) and for conjunctival mast cell numbers. Delayed-phase groups were also examined for eosinophil numbers and for tight junctional protein expression.Results:Olopatadine-treated and alcaftadine-treated animals had similar efficacy profiles and mast cell numbers, suggesting both were effective at ameliorating symptoms of the acute phase. In contrast, alcaftadine-treated animals had significantly lower conjunctival eosinophil infiltration than either controls or olopatadine-treated animals. Allergen challenge caused a significant decrease in expression of the junctional protein, ZO-1, and this decrease was prevented by alcaftadine but not by olopatadine.Conclusion:Alcaftadine displays therapeutic properties beyond its antihistamine action. These include an ability to reduce conjunctival eosinophil recruitment, and a protective effect on epithelial tight junction protein expression.

Adjuvants determine the contribution of basophils to antigen sensitization in vivo

PurposeBasophils expressing FcɛRIα, the alpha chain of the total IgE high affinity receptor, appear to play a role in antigen (Ag) sensitization, although dendritic cells (DCs) are the principal Ag-presenting cells (APCs). To investigate whether these two types of APCs are involved differentially in Ag-sensitization when distinct types of adjuvants are utilized. MethodsTo investigate whether basophils and DCs serve as APCs in vitro, whole splenocytes, FcɛRIα+ basophil-depleted splenocytes, and CD11c+ DC-depleted splenocytes from naïve DO11.10 mice were stimulated in vitro with ovalbumin (OVA) or OVA peptide 323–339 to evaluate Ag-induced proliferation. To investigate whether basophils function as APCs in vivo, BALB/c mice were actively immunized with ragweed (RW) emulsified in alum or Complete Freund's Adjuvant (CFA) followed by an RW challenge in eye drops. An anti-FcɛRIα antibody (Ab) or a control Ab was injected intraperitoneally during the sensitization phase. Twenty-four hours after the RW challenge, conjunctivas and spleens were harvested for histological analysis to evaluate conjunctival eosinophilia and cytokine production, respectively. ResultsDepletion of basophils or DCs from naïve DO11.10 splenocytes significantly suppressed proliferative responses to either OVA or OVA peptide. Treatment with the anti-FcɛRIα Ab suppressed the conjunctival eosinophilia when alum, but not CFA, was utilized as the adjuvant. Similarly, the anti-FcɛRIα Ab inhibited cytokine production by splenocytes when alum was used as the adjuvant. ConclusionAdjuvants determine which APCs are utilized in Ag-sensitization.

Ocular Allergic Inflammation: Interaction between the Cornea and Conjunctiva

Severe ocular allergic diseases such as vernal keratoconjunctivitis are characterized not only by conjunctival allergic inflammation, including infiltration of T helper 2 cells and eosinophils into the conjunctiva, but also by various corneal disorders such as persistent epithelial defects and shield ulcer. Although the cornea and conjunctiva are thought to influence each other during ocular allergic inflammation, direct evidence for interaction between these tissues in vivo has been lacking. Eosinophils and eosinophil-derived factors are implicated in the pathogenesis of corneal lesions associated with ocular allergy, with cytotoxic granule proteins such as major basic protein and matrix metalloproteinase 9 derived from eosinophils having been detected in shield ulcer. Major basic protein exhibits cytotoxic effects in cultured corneal epithelial cells and inhibits corneal epithelial wound healing in organ culture, whereas matrix metalloproteinase 9 can degrade the corneal epithelial basement membrane. In vitro studies have revealed that cytokines and other inflammatory mediators directly impair the barrier function of corneal epithelial cells and increase the expression of chemokines and adhesion molecules by corneal stromal fibroblasts, effects that may enhance allergic inflammation. We have recently shown that removal of the corneal epithelium augmented late-phase clinical signs and conjunctival eosinophilia, whereas conjunctival inflammation delayed corneal epithelial wound healing, in a rat model of ocular allergy. Conjunctival allergic inflammation and corneal epithelial disorders thus interact with each other in vivo to generate a vicious cycle, interruption of which might provide the basis for novel approaches to the treatment of severe ocular allergy.

Atopic keratoconjunctivitis and atopic dermatitis

This review will focus on the diagnostic features of atopic keratoconjunctivitis (AKC), its relationship to atopic dermatitis, the immunopathogenesis, and therapy, and will include strategies used for the management of severe disease unresponsive to conventional therapy. Recent research has demonstrated the importance of various cytokines (IL-33), proteins (thymic stromal lymphopoetin) and effector cells (conjunctival epithelial cells, eosinophils and basophils) in the pathogenesis of chronic ocular inflammation. Current evidence supports the use of tacrolimus and cyclosporin A, topically or systemically, as well tolerated and effective steroid sparing agents. Recalcitrant AKC may be a blinding condition. Understanding the immunopathogenesis of atopic dermatitis and AKC has already influenced therapy and is essential to the development of future immunomodulatory treatments. The successful management of AKC requires the use of topical cromones, antihistamines and calcineurin inhibitors. Severely affected patients also require systemic immunosuppressive therapy. The current challenge is to find more specific topical and systemic immunomodulatory therapies with a better side-effect profile.

Cellular characteristics of non‐allergic eosinophilic conjunctivitis

This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or non-allergic eosinophilic conjunctivitis (NAEC). Fourteen patients with conjunctivitis and eosinophilia in cytology samples were included in the study. Seven had positive skin-prick tests (the AEC group) and seven had negative skin-prick tests (the NAEC group). Eight asymptomatic subjects with negative skin-prick tests served as a control group. In conjunctival biopsies eosinophils were identified with monoclonal antibodies. Mast cells were identified by specific immunostaining and tryptase-positive granules were counted around them. The percentage of degranulated mast cells was used as a measure of cell activation. Eosinophil and goblet cell numbers were counted, epithelial thickness was measured, and the symptoms were characterized and graded. The numbers of eosinophils in biopsies were higher in patients with AEC than in healthy controls (p = 0.010). The proportion of activated mast cells tended to be higher in AEC patients (65%) than in NAEC patients (48%) or control subjects (40%). Patients with AEC had more goblet cells than control subjects (p = 0.049) and their epithelial layer was thicker (p = 0.054). Patients with AEC had more severe symptoms than control subjects (p = 0.0005), whereas the symptoms of NAEC patients did not differ statistically from those of controls (p = 0.065). Patients with NAEC were characterized by mild eosinophilic inflammation and only minor structural conjunctival changes. The condition seems to run a relatively mild but persistent clinical course.

Transfer of a T-helper Type 2 Clone Into Conjunctiva Induces Corneal Damage in Mice

We established a T-helper Type 2 (Th2) clone-induced conjunctival eosinophilia model by injecting D10.G.4.1 (D10) cells, a murine Th2 clone, and conalbumin, its specific antigen, into conjunctiva of AKR/J mice. Using this model, we investigated the effect of a coinjection of D10 cells and conalbumin into conjunctiva on corneal damage. Corneal fluorescein staining scores and eosinophil peroxidase (EPO) activity in conjunctiva were measured after coinjection of D10 and conalbumin into conjunctiva, and the effects of cyclosporine A, betamethasone, and anti-interleukin-5 antibody on staining scores and EPO activity were examined. Coinjection of D10 and conalbumin induced an increase of the corneal fluorescein staining score after 24, 48, and 96 hours and 10 days. EPO activity in conjunctiva increased time-dependently until 24 hours after coinjection. The increase in the staining score followed the time dependent increase in EPO activity. The instillation of cyclosporine A, an inhibitor of cytokine production from T-cells, and betamethasone significantly inhibited the increase in corneal fluorescein score and EPO activity. Intraperitoneal administration of anti-interleukin-5 monoclonal antibody, which inhibits the infiltration of eosinophils into the conjunctiva, completely inhibited the increase in staining score. The transfer of the Th2 clone into the murine conjunctiva induced corneal damage, which may have been caused by Th2 cell-produced interleukin-5 that mediated the activation of eosinophils.

Participation of CD11b and F4/80 Molecules in the Conjunctival Eosinophilia of Experimental Allergic Conjunctivitis

Background: CD11b and F4/80 are macrophage surface markers. How these molecules participate in allergic eosinophil infiltration remains unclear. We examined the roles CD11b and F4/80 play in the conjunctival eosinophil infiltration associated with experimental allergic conjunctivitis. Methods: Ragweed-immunized BALB/c mice were challenged with ragweed in eye drops to induce conjunctival eosinophil infiltration. The effect of challenge on conjunctival CD11b+ and F4/80+ cell numbers was determined by immunohistochemistry. In the same model, blocking anti-CD11b and anti-F4/80 Abs were injected intraperitoneally during the induction or the effector phase, or subconjunctivally 2 h before challenge, to determine their effect on challenge-induced conjunctival eosinophilia. To examine whether eosinophils express CD11b and F4/80 molecules, splenocytes from IL-5 gene-electroporated mice were subjected to flow cytometric analysis. To clarify the involvement of CD11b and F4/80 in conjunctival eosinophil infiltration, mice were intraperitoneally injected with anti-CD11b and anti-F4/80 Abs and then subconjunctivally injected with eotaxin to induce conjunctival eosinophilia. Results: Ragweed challenge elevated conjunctival CD11b+ and F4/80+ cell numbers. Systemic anti-CD11b and anti-F4/80 Ab treatments during the effector phase, but not in either the induction phase or the local injection of Ab, suppressed conjunctival eosinophil infiltration in ragweed-induced conjunctivitis. Most splenic eosinophils from IL-5 gene-introduced mice expressed CD11b and F4/80. Systemic anti-CD11b and anti-F4/80 Ab treatment suppressed conjunctival eosinophilia induced by subconjunctival eotaxin injection. Conclusions: CD11b and F4/80 appear to participate in conjunctival eosinophil infiltration in allergic conjunctivitis. Their involvement in conjunctival eosinophilia appears to be due to their expression on eosinophils rather than on macrophages.

Minimal persistent inflammation in allergic rhinitis: implications for current treatment strategies.

Patients with allergic rhinitis have traditionally been placed into 'seasonal' and 'perennial' categories, which do not account for the subclinical inflammatory state that exists in many patients. In subjects with seasonal and perennial allergic rhinitis, even subthreshold doses of allergen have been found to cause inflammatory cell infiltration in the nasal mucosa, including increases in expression of cellular adhesion molecules, nasal and conjunctival eosinophilia, and other markers of inflammation, which do not result in overt allergy symptoms. This state - which has been termed 'minimal persistent inflammation'- may contribute to hyperreactivity and increased susceptibility to development of clinical symptoms as well as common co-morbidities of allergic rhinitis, such as asthma. Treating overt allergy symptoms as well as this underlying inflammatory state requires agents that have well-established clinical efficacy, convenient administration, potent anti-inflammatory effects and proven long-term safety, so that long-term continuous administration is feasible. Of the three major classes of commonly used allergic rhinitis medications - intranasal corticosteroids, anti-histamines, and anti-leukotrienes - intranasal corticosteroids appear to represent the most reasonable therapeutic option in patients who would benefit from continuous inhibition of persistent inflammation.

Systemic overexpression of IFN-γ and IL-5 exacerbates early phase reaction and conjunctival eosinophilia, respectively, in experimental allergic conjunctivitis

Aims/background:To investigate how systemic overexpression of IL-4, IL-5 and IFN-γ affects the severity of experimental conjunctivitis (EC) in mice.Methods:The tibialis anterior muscle of naive BALB/c mice was electroporated with IL-4,...

Treatment with FTY720 during the induction or effector phase suppresses the development of experimental allergic conjunctivitis in mice

To investigate whether experimental allergic conjunctivitis (EC) can be suppressed by treatment with the immunomodulatory drug FTY720, which reduces the recruitment of effector T cells into inflammatory sites. BALB/c mice were actively immunized with ragweed (RW) and then injected intraperitoneally with FTY720 on days 0, 2, 4, 6 and 8 (induction phase treatment) followed by challenge on day 10 with RW-containing eye drops. Alternatively, naïve mice that received RW-primed splenocytes were injected intraperitoneally with FTY720 on days 2 and 4 (effector phase treatment) followed by RW challenge on day 4. Twenty-four hours after RW challenge, conjunctivas and spleens were harvested for histology or immunohistochemistry, and flow cytometric analysis or cytokine assays, respectively. FTY720 treatment during the induction phase suppressed the conjunctival infiltration of T cells as well as eosinophils and macrophages. The splenocytes from induction phase-treated mice contained significantly less CD4(+) and CD8(+) T cells and showed significant suppression of Th2 but not Th1 cytokine production. Effector phase treatment with FTY720 suppressed conjunctival eosinophil infiltration. These data demonstrate that FTY720 treatment during the induction phase decreases the absolute number of CD4(+) and CD8(+) T cells in the spleen and suppresses Th2 cytokine production by splenocytes. This leads to the suppression of EC. FTY720 treatment also suppresses EC when delivered during the effector phase. Thus, FTY720 treatment may be suitable for treating severe forms of vernal keratoconjunctivitis.