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.

Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients.

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

Intralymphatic immunotherapy improves grass pollen allergic rhinoconjunctivitis: A 3-year randomized placebo-controlled trial.

BACKGROUND: Allergic rhinoconjunctivitis is a global health problem. Different allergen immunotherapy regimes are marketed but have low adherence because they are expensive, complex, and time-consuming. New allergen immunotherapy forms are needed. OBJECTIVE: In a 3-year follow-up double-blind randomized placebo-controlled trial, we aimed to investigate the effect of intralymphatic allergen immunotherapy (ILIT). METHODS: Patients with grass pollen rhinoconjunctivitis were treated with 3 ILIT injections and an ILIT booster 1 year later, 3 ILIT injections and a placebo booster, or 3 placebo injections and a placebo booster. Primary outcome was improvement in a combined symptom and medication score (cSMS). A novel evaluation tool with a linear regression model of cSMS and grass pollen counts was developed. Secondary outcomes were changes in grass specific immunoglobulins and skin and nasal provocation tests to grass pollen. RESULTS: A total of 36 patients were included. Log10-transformed cSMS was reduced by 0.30 (95% CI, 0.11-0.49; P = .002), equaling 48.5% (95% CI, 24.5%-62%), in the entire 3-year follow-up period, significant only in the first follow-up season but not in the second and third seasons. The regression model showed a 37% (P < .001) reduction in cSMS. The booster injection 1 year later had no additional effect. Secondary, repeated measures of IgE and IgG4 to grass showed significant between-group difference and within-group change in the ILIT groups. No change in provocation test results was found. CONCLUSIONS: ILIT gives a substantial reduction in grass pollen allergy symptoms and use of rescue medication, significant in the first season after treatment. A booster injection had no additional effect.

Experimental Mouse Models of Ragweed- and Papain-Induced Allergic Conjunctivitis.

Mouse models of allergic conjunctivitis mimic various aspects of human allergic conjunctivitis. They are useful as acute models of allergic conjunctivitis to study immunological aspects of this condition. In this chapter, we will describe ragweed-pollen-induced experimental allergic conjunctivitis (mostly driven by adaptive immunity), and papain-soaked contact lens-induced experimental allergic conjunctivitis (mostly driven by innate immunity). Giemsa staining of histological sections is used for quantification of the number of infiltrating eosinophils, which is useful to evaluate the severity of the allergic inflammation. Immunohistochemical staining and quantitative PCR are used to clarify spatiotemporal expression of proinflammatory molecules in the conjunctival tissue. Flow cytometric analysis of conjunctival tissue is used for the detection of innate lymphoid cell type 2 (ILC2) in the ocular surface tissues.

Intradermal Phleum pratense allergoid immunotherapy. Double-blind, randomized, placebo-controlled trial.

BACKGROUND: In allergology, the intradermal approach is generally used to establish an aetiological diagnosis, with limited experience in specific allergen immunotherapy. OBJECTIVE: To evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde-polymerized Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen. METHODS: Multicentre, randomized, double-blind, placebo-controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of six doses in a weekly interval, of either placebo; 0.03 or 0.06 µg of protein per dose of P pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale. RESULTS: The dose of 0.06 µg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded. CONCLUSION & CLINICAL RELEVANCE: Intradermal immunotherapy with P pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.

Compliance in subcutaneous and sublingual allergen immunotherapy: A nationwide study.

INTRODUCTION: Allergic rhino-conjunctivitis is a highly prevalent condition. In moderate to severe cases, allergen immunotherapy (AIT) is a cost-effective therapeutic option. Previous data have reported a large difference in treatment compliance of subcutaneously (SCIT) and sublingually (SLIT) administered AIT. METHODS: By use of the unique civil registration number assigned to all Danish citizens and the Danish National Health Service Prescription Database, compliance rates of all patients prescribed with grass pollen AIT from January 1998 until December 2016 were analysed annually during the three-year treatment period. RESULTS: The male/female ratio was close to 1:1 in SCIT, while SLIT was more frequently used by men. A large proportion of users was children or adolescents (32% and 45%, SCIT and SLIT, respectively). Compliance of both subcutaneous and sublingual treatment gradually fell each year; compliance in year 3 was 57% and 53% for subcutaneous and sublingual treatment, respectively. Compliance of grass pollen sublingual treatment was also analysed each year after registration on the Danish market. Compliance significantly increased following the introduction and stabilised on a relatively high level. CONCLUSION: Based on previous studies, we hypothesised that AIT compliance would be low, especially in SLIT. However, in Denmark, compliance in SCIT and SLIT was almost similar, and the majority of patients completed the three-year treatment period with a compliance in the last quintile.

The allergic eye: recommendations about pharmacotherapy and recent therapeutic agents.

PURPOSE OF REVIEW: Ocular allergies affect an estimated 40% of the population, 98% of which are because of allergic conjunctivitis. With the current advent of both repurposed drugs for ocular allergies, as well as novel drugs and methods of administration, there is a need for an updated review of current available medications. A clear characterization of each treatment will ultimately allow treating physicians to restore patients' quality of life and decrease burden of disease. RECENT FINDINGS: Currently, there are a number of reformulated antihistamines, with cetrizine being the most recent ophthalmic solution available. Nevertheless, there is ongoing research in the field of immunotherapy, steroids, flavonoids, cannabis, and drug-delivery systems. SUMMARY: Although dual-activity agents remain the keystone for treatment, newer drugs and drug-delivery systems offer other novel directions for delivering appropriate relief with minimal adverse effects.

Association of early viral lower respiratory infections and subsequent development of atopy, a systematic review and meta-analysis of cohort studies.

INTRODUCTION: Existing evidence on the relationship between childhood lower respiratory tract infections (LRTI) and the subsequent atopy development is controversial. We aimed to investigate an association between viral LRTI at <5 years and the development of atopy at > 2 years. METHODS: We conducted a search at Embase, Pubmed, Web of Science, and Global Index Medicus. We collected data from the included articles. We estimated the odds ratio and the 95% confidence intervals with a random effect model. We determined factors associated with atopy development after childhood LRTI using univariate and multivariate meta-regression analyses. We recorded this systematic review at PROSPERO with the number CRD42018116955. RESULTS: We included 24 studies. There was no relationship between viral LRTI at <5 years and skin prick test-diagnosed-atopy (OR = 1.2, [95% CI = 0.7-2.0]), unknown diagnosed-atopy (OR = 0.7, [95% CI = 0.4-1.3]), atopic dermatitis (OR = 1.2, [95% CI = 0.9-1.6]), hyperreactivity to pollen (OR = 0.8, [95% CI = 0.3-2.7]), food (OR = 0.8, [95% CI = 0.3-2.5]), or house dust mite (OR = 1.1, [95% CI = 0.6-2.2]). Although not confirmed in all studies with a symmetric distribution of the 23 confounding factors investigated, the overall analyses showed that there was a relationship between childhood viral LRTI at < 5 years and serum test diagnosed-atopy (OR = 2.0, [95% CI = 1.0-4.1]), allergic rhinoconjunctivitis (OR = 1.7, [95% CI = 1.1-2.9]), hyperreactivity diagnosed by serum tests with food (OR = 5.3, [1.7-16.7]) or inhaled allergens (OR = 4.2, [95% CI = 2.1-8.5]), or furred animals (OR = 0.6, [95% CI = 0.5-0.9]). CONCLUSION: These results suggest that there is no association between viral LRTI at < 5 years and the majority of categories of atopy studied during this work. These results, however, are not confirmed for the remaining categories of atopy and more particularly those diagnosed by serum tests. There is a real need to develop more accurate atopy diagnostic tools.

The Potential Inhibitory Effects of miR-19b on Ocular Inflammation are Mediated Upstream of the JAK/STAT Pathway in a Murine Model of Allergic Conjunctivitis.

Purpose: Thymic stromal lymphopoietin (TSLP) is a pro-allergic cytokine that initiates allergic inflammatory reaction between epithelial and dendritic cells (DCs). miR-19b was reported to suppress TSLP expression. The present study aimed to examine miR-19b expression, regulation, and function in allergic conjunctivitis (AC). Methods: A murine model of experimental AC was induced in BALB/c mice by short ragweed pollen. The serum, eye balls, conjunctiva, and cervical lymph nodes (CLN) were used for the study. Gene expression was determined by RT-PCR, whereas protein production and activation were evaluated by immunostaining, ELISA, and Western blotting. Results: In the murine AC model, miR-19b was aberrantly downregulated, whereas the levels of TSLP and p-STAT3, as well as the number of CD11c+ pSTAT3+ DCs were increased. Moreover, Th2 inflammatory cytokine expression was significantly increased. These severe phenotypes could be counteracted by either applying exogenous miR-19b mimic microRNAs or the JAK/STAT inhibitor CYT387. Moreover, overexpression of miR-19b repressed p-STAT3 expression and the number of CD11c+ cells in AC eye and CLN tissues. Conclusions: These findings suggested that miR-19b reduced ocular surface inflammation by inhibiting Stat3 signaling via TSLP downregulation in a murine AC model. Moreover, the present study further demonstrated the clinical potential of applying miR-19b and anti-JAK/STAT therapies in the treatment of AC.

Accelerated Dose Escalation with Three Injections of an Aluminum Hydroxide-Adsorbed Allergoid Preparation of Six Grasses Is Safe for Patients with Moderate to Severe Allergic Rhinitis.

Only few data on safety during high-dose, accelerated escalation schedules during subcutaneous allergen immunotherapy (AIT) are available. The aim of this study was to assess the safety and tolerability of an accelerated dose escalation schedule of AIT in adult patients with moderate to severe seasonal rhinoconjunctivitis in a multicenter, open-label, randomized phase II trial. The dose escalation scheme for patients in Group I (1 strength) included 3 injections with 1 strength, B (10,000 TU/mL), whereas the dose escalation scheme for Group II (standard) included 7 injections with 2 strengths, A (1,000 TU/mL) and B (10,000 TU/mL), of an aluminum hydroxide-adsorbed allergoid grass pollen preparation. Overall, 72 of 87 randomized patients (83.7%) reported at least 1 treatment-emergent adverse event (TEAE; 82.2 [Group I] vs. 85.4% [Group II]); 58.8% of all reported TEAEs were assessed as being related to AIT (60.0 vs. 48.8%). The most frequently reported AIT-related TEAEs were swelling (46.7 vs. 34.1%), erythema (28.9 vs. 36.6%), and pruritus (31.1 vs. 17.1%) at the site of the injection. Systemic allergic reactions occurred in 5 (5.8%) patients overall, with more being reported in the 1-strength group (4 [8.9%] vs. 1 [2.4%]). All systemic allergic reactions were classified as World Allergy Organization (WAO) Grade 1 or Grade 2 reactions. Accelerated high-dose escalation with an aluminum hydroxide-adsorbed grass pollen allergoid can be initiated with a safety and tolerability profile comparable to the standard dose escalation schedule in patients with allergic rhinitis with or without asthma.

Clinical assessment of tolerability, immunological and cutaneous reactivity effects of an abbreviated schedule with Olea europaeanative extract of subcutaneous immunotherapy.

Summary: Objectives. To evaluate the tolerability and efficacy of Olea europaea subcutaneous immunotherapy (SCIT) on patients with rhinoconjunctivitis. Methods. In this open clinical trial patients were assigned to an abbreviated build-up scheme. The outcomes were: number, percentage, and severity of adverse reactions. Secondary outcomes included: changes in immunoglobulin titers and changes in dose-response skin prick tests. Results. Only 8 systemic reactions were registered, which represented 7/47 (14.9%) of patients and 8/429 (1.9%) of administered doses. Regarding immunological parameters the significant increases of sIgG and sIgG4 evidenced the changes in the patient immune system. Cutaneous reactivity decreased significantly. Conclusions. Olea europaea SCIT (Allergovac® depot ROXALL Medicina España S.A.) showed a good safety and tolerability profile. Immunological changes with induction of blocking IgG and decreases in cutaneous reactivity were detected in the patients.

Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial.

Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.

Pollen-Food Allergy Syndrome: A not so Rare Disease in Childhood.

Seasonal allergic rhinoconjunctivitis (SAR) affects millions of people worldwide, particularly in childhood and adolescence. Pollen food allergy syndrome (PFAS) is a common adverse reaction occurring few minutes after the consumption of vegetable foods in patients with pollen-induced SAR. PFAS has rarely been investigated in the pediatric population, as it has been mainly examined as an adult disease. Recent studies suggested that PFAS might be more frequent in childhood than previously recognized. The present review aims to give an overview of the epidemiology, pathophysiology, diagnosis, management and prognosis of PFAS in children with SAR-induced by pollens.

The roles of omega-3 fatty acids and resolvins in allergic conjunctivitis.

PURPOSE OF REVIEW: Lipids are one of the most important constituents in our body. Advances of lipidomics are elucidating the new roles of various lipid molecules in allergic diseases. For example, some reports showed anti-inflammatory effects of omega-3 fatty acids (FAs), such as docosahexaenoic acid, eicosapentaenoic acid, and their metabolites, on allergic diseases. Here, we introduce the role of lipid mediators in allergic conjunctivitis mouse model. RECENT FINDINGS: Lipidomics using liquid chromatography-tandem mass spectrometry can profile numerous lipid molecules from small tissue samples such as conjunctival specimens. Lipidomics analysis showed that various inflammatory lipid mediators are produced in the conjunctival tissue of allergic conjunctivitis mouse model. Dietary omega-3 FAs reduced these inflammatory lipid mediators in the conjunctiva and alleviated allergic conjunctivitis symptoms in mouse models. In addition, the roles of specialized proresolving lipid mediators (SPMs) have been reported for allergic inflammation. SUMMARY: Lipid mediators have important roles for the pathophysiology of the allergic diseases including allergic conjunctivitis. Omega-3 FAs and SPMs are expected as new treatment tools for allergic conjunctivitis.

Real-life safety of 5-grass pollen tablet in 5-to-9-year-old children with allergic rhinoconjunctivitis.

BACKGROUND: Although 5-grass pollen sublingual immunotherapy has a good safety profile in controlled clinical trials, additional safety information among pediatric patients in a real-world setting would be useful. OBJECTIVE: To further document the safety of 5-grass tablet among children aged 5 to 9 years with allergic rhinoconjunctivitis (ARC). METHODS: This multicenter, observational study included allergy immunotherapy-naïve 5- to 9-year-old children with grass pollen-induced ARC prescribed with 5-grass tablet daily (3-day dose escalation to 300 index of reactivity [IR]). Patients were followed up daily for safety and tolerability over the first 30 treatment days. Adverse events (AEs) and adverse drug reactions (ADRs) were analyzed descriptively. RESULTS: Three hundred seven children (mean age, 7.1 years) were enrolled. Fifty-eight percent were confirmed as polysensitized, and 36% had mild-to-moderate asthma. Of 307 patients, 233 (76%) reported AEs, and 173/307 (56%) reported ADRs, most frequently mild application-site reactions (throat irritation, oral pruritus, oral paresthesia). Sixteen of 307 (5.2%) patients withdrew because of ADRs. In 143 of 173 (83%) patients, ADRs first occurred within 1 week of starting treatment. More than half of the ADRs lasted less than 2 days, and ADRs resolved spontaneously in 161 of 173 (93%) patients. Recurrences of ADRs were reported in 45 of 173 (26%) patients and were also mainly application-site reactions. No notable differences were found in ADRs related to whether patients had asthma at inclusion. Neither epinephrine use nor admission to intensive care unit was reported. CONCLUSION: The safety profile of 5-grass tablet in pediatric ARC patients aged 5 to 9 years was consistent with safety findings in older patients, most ADRs being at the application site and mild to moderate. ClinicalTrials.gov identifier: NCT02295969; EUPAS registration number: 8104.

Clinical standardization of two controlled allergen challenge facilities: The Environmental Exposure Unit and the Biogenics Research Chamber.

BACKGROUND: Controlled allergen challenge facilities (CACF), in disparate geographic regions with dissimilar engineering and base populations, have historically functioned as single, independent sites in clinical allergy trials. We aimed to demonstrate "between-unit reproducibility" to allow controlled challenge trials of participants using 2 CACFs. OBJECTIVE: To compare and standardize 2 CACFs located in Kingston, Ontario, Canada, and San Antonio, Texas, by examining participant-reported symptom severity during qualifying and treatment visits and evaluating response to treatment, while using the same allergen. METHODS: At 2 different CACFs, participants were enrolled in a double-blind, placebo-controlled, crossover intervention trial with cetirizine 10 mg. Different distribution devices delivered common short ragweed pollen via laminar air flow and maintained an airborne concentration of 3500 ± 700 grains/m3 in both facilities. A 1-hour "sham" run with no pollen release preceded a priming exposure of 3 hours and was followed 3 days later by a qualifying/treatment 5-hour exposure. At least 14 days later, another priming exposure was followed by the crossover exposure and treatment. RESULTS: Forty-eight and 43 subjects completed the study at Kingston and San Antonio, respectively. Demographics were similar. Fewer than 10% exhibited symptoms with sham exposure. No significant differences were found between the 2 facilities in maximal total rhinoconjunctivitis symptom score, total nasal symptom score, and total ocular symptom score, nor in areas under the curve. In both facilities, no significant effects of cetirizine 10 mg over placebo were detected. CONCLUSION: The results were equivalent, demonstrating that the 2 CACFs can be used together in dual-center clinical trials and show the possibility of multicenter trials involving multiple CACFs.

Periostin deletion suppresses late-phase response in mouse experimental allergic conjunctivitis.

BACKGROUND: To investigate the potential roles of periostin (POSTN), an extracellular matrix preferentially expressed in Th2-skewed conditions in the pathophysiology of allergic conjunctivitis. METHODS: The roles of POSTN in ragweed-induced experimental allergic conjunctivitis (RW-EAC) were evaluated using both POSTN-knockout (KO) and congenic BALB/c wild-type mice. Histological analysis was carried out to enumerate eosinophils/basophils in the conjunctival tissue. Th2 cytokine expression was evaluated by quantitative polymerase chain reaction (Q-PCR), and microarray analysis was performed to elucidate genes differentially expressed in POSTN-KO and wild-type mice in the RW-EAC model. RESULTS: Upregulation of POSTN expression and eosinophil infiltration was observed in subconjunctival tissue of RW-EAC in the wild-type mice. The number of infiltrating eosinophils in the conjunctivae of RW-EAC was diminished in POSTN-KO mice compared to wild-type mice. Q-PCR analysis of conjunctival tissue showed induction of Th2 cytokine (Ccl5, Il4, Il5, Il13) expression in the RW-EAC and attenuated Ccl5, Il4, Il13 mRNA expression in the conjunctivae of the RW-EAC using POSTN-KO mice. Microarray analysis and immunohistochemical analysis showed diminished basophil marker (Mcpt8) expression and reduced numbers of infiltrating basophils in the conjunctivae of RW-EAC in POSTN-KO mice. CONCLUSIONS: POSTN expression in conjunctival tissue plays an indispensable role in the late-phase reaction of the RW-EAC model by facilitating eosinophil/basophil infiltration and augmenting Th2 cytokine expression.

Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.

Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (Th2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting Th2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of Th2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6-derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet-fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.-Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.

Seasonal ocular allergy and pollen counts.

PURPOSE OF REVIEW: The purpose of the article is to provide a historical overview of literature regarding pollen sensitization and ocular allergy with an emphasis on developments that have occurred over the past 5 years. RECENT FINDINGS: Currently, pollen studies have examined the molecular and cellular pathways involved in initiating allergic conjunctivitis to find targets for therapeutics. Studies have also documented the threshold, linear increase and plateau point in the relationship between pollen levels and allergic conjunctivitis symptoms. SUMMARY: Traditionally, intact pollen grains are counted as a means of correlating patient symptoms to allergen exposure. However, establishing a dose-response relationship between pollen grain exposure and allergic conjunctivitis has proven to be difficult. It has been observed that ocular allergies induce a two-fold response including early-phase and late-phase IgE-mediated reactions. Sensitization itself is a combination of pollen exposure over time in genetically predisposed individual. However, symptoms appear to reach an asymptotic point at which clinical severity plateaus. More studies are needed to clearly define differences in pollen sensitization by plant species.