A pilot randomized clinical trial of γ-tocopherol supplementation on wood smoke-induced neutrophilic and eosinophilic airway inflammation.

Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation. Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans. Methods: This was a randomized, placebo-controlled clinical trial testing the effect of a short course of γ-tocopherol-enriched supplementation on airway inflammation following a controlled exposure to wood smoke particulates. Results: Short-course γ-tocopherol intervention did not reduce wood smoke-induced neutrophilic airway inflammation, but it did prevent wood smoke-induced eosinophilic airway inflammation. Conclusion: γ-Tocopherol is a potential intervention for exacerbation of allergic airway inflammation, but further study examining longer dosing periods is required.

Gamma-tocopherol, a major form of vitamin E in diets: Insights into antioxidant and anti-inflammatory effects, mechanisms, and roles in disease management.

γ-Tocopherol (γT) is a major form of vitamin E in the US diet and the second most abundant vitamin E in the blood and tissues, while α-tocopherol (αT) is the predominant vitamin E in tissues. During the last >25 years, research has revealed that γT has unique antioxidant and anti-inflammatory activities relevant to disease prevention compared to αT. While both compounds are potent lipophilic antioxidants, γT but not αT can trap reactive nitrogen species by forming 5-nitro-γT, and appears to show superior protection of mitochondrial function. γT inhibits ionophore-stimulated leukotrienes by blocking 5-lipoxygenase (5-LOX) translocation in leukocytes, decreases cyclooxygenase-2 (COX-2)-catalyzed prostaglandins in macrophages and blocks the growth of cancer cells but not healthy cells. For these activities, γT is stronger than αT. Moreover, γT is more extensively metabolized than αT via cytochrome P-450 (CYP4F2)-initiated side-chain oxidation, which leads to formation of metabolites including 13'-carboxychromanol (13'-COOH) and carboxyethyl-hydroxychroman (γ-CEHC). 13'-COOH and γ-CEHC are shown to be the predominant metabolites found in feces and urine, respectively. Interestingly, γ-CEHC has natriuretic activity and 13'-COOH inhibits both COX-1/-2 and 5-LOX activity. Consistent with these mechanistic findings of γT and metabolites, studies show that supplementation of γT mitigates inflammation and disease symptoms in animal models with induced inflammation, asthma and cancer. In addition, supplementation of γT decreased inflammation markers in patients with kidney diseases and mild asthma. These observations support that γT may be useful against inflammation-associated diseases.

Acute asthma management during SARS-CoV2-pandemic 2020.

BACKGROUND: The current COVID-19 pandemic has changed many medical practices in order to provide additional protection to both our patients and healthcare providers. In many cases this includes seeing patients through electronic means such as telehealth or telephone rather than seeing them in person. Asthma exacerbations cannot always be treated in this way. PROBLEM: Current emergency unit asthma guidelines recommend bronchodilators be administered by metered dose inhaler (MDI) and spacer for mild-moderate asthma and include it as a choice even in severe asthma, but many emergency units continue to prefer nebulised therapy for patients who urgently require beta-agonists. The utilization of nebulised therapy potentially increases the risk of aerosolization of the coronavirus. Since nosocomial transmission of respiratory pathogens is a major threat in the context of the SARS-CoV-2 pandemic, use of nebulised therapy is of even greater concern due to the potential increased risk of infection spread to nearby patients and healthcare workers. PRACTICAL IMPLICATIONS: We propose a risk stratification plan that aims to avoid nebulised therapy, when possible, by providing an algorithm to help better delineate those who require nebulised therapy. Protocols that include strategies to allow flexibility in using MDIs rather than nebulisers in all but the most severe patients should help mitigate this risk of aerosolised infection transmission to patients and health care providers. Furthermore, expedient treatment of patients with high dose MDI therapy augmented with more rapid initiation of systemic therapy may help ensure patients are less likely to deteriorate to the stage where nebulisers are required.

Emerging concepts and challenges in implementing the exposome paradigm in allergic diseases and asthma: a Practall document.

Exposome research can improve the understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the life span. The exposomic approach provides a risk profile instead of single predictors and thus is particularly applicable to allergic diseases and asthma. Under the PRACTALL collaboration between the European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma, and Immunology (AAAAI), we evaluated the current concepts and the unmet needs on the role of the exposome in allergic diseases and asthma.

Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma.

BACKGROUND: We and others have shown that the gamma tocopherol (γT) isoform of vitamin E has multiple anti-inflammatory and antioxidant actions and that γT supplementation reduces eosinophilic and endotoxin (LPS)-induced neutrophilic airway inflammation in animal models and healthy human volunteers. OBJECTIVE: We sought to determine whether γT supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma. METHODS: Participants with mild asthma were enrolled in a double-blinded, placebo-controlled crossover study to assess the effect of 1200 mg of γT daily for 14 days on sputum eosinophils, mucins, and cytokines. We also assessed the effect on acute inflammatory response to inhaled LPS challenge following γT treatment, focusing on changes in sputum neutrophilia, mucins, and cytokines. Mucociliary clearance was measured using gamma scintigraphy. RESULTS: Fifteen subjects with mild asthma completed both arms of the study. Compared with placebo, γT notably reduced pre-LPS challenge sputum eosinophils and mucins, including mucin 5AC and reduced LPS-induced airway neutrophil recruitment 6 and 24 hours after challenge. Mucociliary clearance was slowed 4 hours postchallenge in the placebo group but not in the γT treatment group. Total sputum mucins (but not mucin 5AC) were reduced at 24 hours postchallenge during γT treatment compared with placebo. CONCLUSIONS: When compared with placebo, γT supplementation for 14 days reduced inflammatory features of asthma, including sputum eosinophils and mucins, as well as acute airway response to inhaled LPS challenge. Larger scale clinical trials are needed to assess the efficacy of γT supplements as a complementary or steroid-sparing treatment for asthma.

A proof-of-concept clinical study examining the NRF2 activator sulforaphane against neutrophilic airway inflammation.

UNLABELLED: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, is implicated as a possible therapy for airway inflammation via induction of the transcription factor NF-E2-related factor 2 (NRF2). In this proof-of-concept clinical study, we show that supplementation of SFN with broccoli sprout homogenate in healthy human subjects did not induce expression of antioxidant genes or protect against neutrophilic airway inflammation in an ozone-exposure model. Therefore, dietary sulforaphane supplementation is not a promising candidate for larger scale clinical trials targeting airway inflammation. TRIAL REGISTRATION: NCT01625130 . Registered 19 June, 2012.

Supplementation with γ-tocopherol attenuates endotoxin-induced airway neutrophil and mucous cell responses in rats.

Neutrophil-mediated tissue injury is a shared pathogenesis of both chronic pulmonary diseases and acute responses to pathogens, allergens, and airborne pollutants. Interventions to minimize toxic effects of neutrophil-derived oxidants and proteases are usually limited to corticosteroids, which can have adverse side effects. We used a rodent model of endotoxin-induced lung injury to test the hypothesis that the dietary supplement γ-tocopherol (γT), a natural form of vitamin E with antioxidant and novel anti-inflammatory properties, will protect from adverse nasal and pulmonary inflammatory responses induced by endotoxin (lipopolysaccharide; LPS). Male Fisher F344 rats were intranasally (i.n.) instilled with LPS for 2 consecutive days. Beginning 2 days before i.n. LPS, the rats were gavaged daily with 30mg/kg γT. Twenty-four hours after the last i.n. LPS, bronchoalveolar lavage fluid (BALF) was collected, and pulmonary and nasal tissues were analyzed for gene expression and morphometric analyses of neutrophils and intraepithelial mucosubstances (IM). LPS caused increased BALF total cells (70% increase), neutrophils (300%), protein (35%), PGE2 (500%), and secreted mucins (75%). Robust increases in neutrophils and IM were detected in conducting airways. Pulmonary expression of MUC5AC, MIP-2, CINC-1, and MCP-1 was elevated three- to eightfold by LPS. Treatment with γT inhibited LPS-induced increases in BALF total cells, neutrophils, protein, PGE2, and secreted mucins, as well as IM and tissue neutrophil influx. Furthermore γT induced the expression of the regulatory cytokines IL-10 and IFN-γ while decreasing MUC5AC, MIP-2, CINC-1, and MCP-1. These data demonstrate novel therapeutic effects of the dietary vitamin E γT promoting anti-inflammatory pathways to protect from neutrophil-mediated lung injury.

Effects of ex vivo γ-tocopherol on airway macrophage function in healthy and mild allergic asthmatics.

Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate γ-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6) and mild house dust mite-sensitive allergic asthmatics (n = 6) were treated ex vivo with GT (300 µM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and decreased (p < 0.05) macrophage expression of CD206, CD36 and CD86 in allergic asthmatics but not in controls. Overall, GT caused downregulation of both innate and adaptive immune response elements, and atopic status appears to be an important factor.

Vitamin E, γ-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers.

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (γ-tocopherol, γT) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether γT supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. F344/N rats were randomized to oral gavage with γT versus placebo, followed by intranasal LPS (20µg) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo-controlled crossover study in which they consumed either a γT-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 h after inhaled LPS. The effect of γT compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. In rats, oral γT supplementation significantly reduced tissue infiltration (p<0.05) and accumulation of airway neutrophils (p<0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, γT treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Oral supplementation with γT reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that γT is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations.

Advances in environmental and occupational respiratory diseases in 2009.

The year 2009 led to a number of significant advances in environmental and occupational allergic diseases. The role of exposure to environmental pollutants, respiratory viruses, and allergen exposure showed significant advances. New allergens were identified. Occupational asthma and the relationship of complementary and alternative medicine to allergic diseases were extensively reviewed. New approaches to immunotherapy, novel vaccine techniques, and methods to reduce risks for severe allergic disease were addressed.

Environmental and occupational allergies.

Airborne allergens are the major cause of allergic rhinitis and asthma. Daily exposure comes from indoor sources, chiefly at home but occasionally at schools or offices. Seasonal exposure to outdoor allergens, pollens, and molds is another important source. Exposure to unusual substances at work causes occupational asthma, accounting for about 5% of asthma in adults. Indoor and outdoor air pollutants trigger airway inflammation and increase the severity of asthma. Diesel exhaust particles increase the production of IgE antibodies. Identification and reduction of exposure to allergens is a very important part of the management of respiratory allergic diseases. The first section of this chapter discusses domestic allergens, arthropods (mites and cockroaches), molds, and mammals (pets and mice). Indoor humidity and water damage are important factors in the production of mite and mold allergens, and discarded human food items are important sources of proliferation of cockroaches and mice. Means of identifying and reducing exposure are presented. The second section discusses outdoor allergens: pollens and molds. The particular plants or molds and the amount of exposure to these allergens is determined by the local climate, and local pollen and mold counts are available to determine the time and amount of exposure. Climate change is already having an important effect on the distribution and amount of outdoor allergens. The third section discusses indoor and outdoor air pollution and methods that individuals can take to reduce indoor pollution in addition to eliminating cigarette smoking. The fourth section discusses the diagnosis and management of occupational asthma.

Gamma-tocopherol attenuates ozone-induced exacerbation of allergic rhinosinusitis in rats.

Compared to healthy subjects, individuals with allergic airway disease (e.g., asthma, allergic rhinitis) have enhanced inflammatory responses to inhaled ozone. We created a rodent model of ozone-enhanced allergic nasal responses in Brown Norway rats to test the therapeutic effects of the dietary supplement gamma-tocopherol (gammaT). Ovalbumin (OVA)-sensitized rats were intranasally challenged with 0% or 0.5% OVA (in saline) on Days 1 and 2, and then exposed to 0 or 1 ppm ozone (eight hours/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg gammaT (p.o., in corn oil) on days 2 through 5, beginning twelve hours after the last OVA challenge. On Day 6, nasal tissues were collected for histological evaluation and morphometric analyses of intraepithelial mucosubstances (IM) and eosinophilic inflammation. Nasal septal tissue was microdissected and analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) for mucin glycoprotein 5AC (MUC5AC) expression levels. Histological analysis revealed mild to moderate eosinophil influx in the mucosa lining the nasal airways and maxillary sinus of OVA-challenged rats (eosinophilic rhinosinusitis). Ozone exposure of allergic rats further increased eosinophils in the maxillary sinus (400%), nasolacrimal duct (250%), and proximal midseptum (150%). Storage of intraepithelial mucosubstances (IM) was not significantly affected by OVA challenge in filtered air-exposed rats, but it was increased by ozone in the septum (45%) and maxillary sinus (55%) of allergic compared to control rats. Treatment with gammaT attenuated the ozone/ OVA-induced synergistic increases in IM and mucosal eosinophils in both nasal and paranasal airways. gamma-Tocopherol also blocked OVA and ozone-induced MUC5AC gene expression. Together, these data describe a unique model of ozone enhancement of allergic rhinosinusitis and the novel therapeutic efficacy of a common supplement, gammaT, to inhibit ozone exacerbation of allergic airway responses.

Combination treatment with high-dose vitamin C and alpha-tocopherol does not enhance respiratory-tract lining fluid vitamin C levels in asthmatics.

Oxidative stress plays a significant role in allergic airway inflammation. Supplementation with alpha-tocopherol (alone or combined with ascorbate/vitamin C) has been assessed as an intervention for allergic airway diseases with conflicting results. Enhancing levels of airway antioxidants with oral supplements has been suggested as an intervention to protect individuals from the effect of inhaled oxidants, although it is unclear whether supplementation changes tocopherol or vitamin C levels in both serum and airway fluids. Our objective was to obtain pilot safety and dosing data from 14 allergic asthmatic volunteers examining the effect of daily combination oral therapy with 500 mg alpha-tocopherol (alpha T) and 2 g vitamin C for 12 wk. We examined serum and airway fluid and cellular levels of alpha- and gamma-tocopherol (gamma T) and vitamin C to plan for future studies of these agents in asthma and allergic rhinitis. Six volunteers completed 12 wk of active treatment with alpha T and vitamin C and 8 completed placebo. Blood and sputum samples were obtained at baseline and at 6 wk and 12 wk of therapy and were analyzed for alpha T, gamma T, and vitamin C levels in the serum, sputum supernatant, and sputum cells. Combination treatment increased serum vitamin C and significantly decreased sputum alpha T and serum gamma T levels. No changes were found in sputum supernatant or sputum cell vitamin C or serum alpha T levels in the active treatment group. In conclusion, supplementation with alpha T and high-dose vitamin C does not augment vitamin C levels in the respiratory-tract lining fluid.

Climate change and allergic disease.

Climate change is potentially the largest global threat to human health ever encountered. The earth is warming, the warming is accelerating, and human actions are largely responsible. If current emissions and land use trends continue unchecked, the next generations will face more injury, disease, and death related to natural disasters and heat waves, higher rates of climate-related infections, and wide-spread malnutrition, as well as more allergic and air pollution-related morbidity and mortality. This review highlights links between global climate change and anticipated increases in prevalence and severity of asthma and related allergic disease mediated through worsening ambient air pollution and altered local and regional pollen production. The pattern of change will vary regionally depending on latitude, altitude, rainfall and storms, land-use patterns, urbanization, transportation, and energy production. The magnitude of climate change and related increases in allergic disease will be affected by how aggressively greenhouse gas mitigation strategies are pursued, but at best an average warming of 1 to 2 degrees C is certain this century. Thus, anticipation of a higher allergic disease burden will affect clinical practice as well as public health planning. A number of practical primary and secondary prevention strategies are suggested at the end of the review to assist in meeting this unprecedented public health challenge.

Sublingual-oral administration of standardized allergenic extracts: phase 1 safety and dosing results.

BACKGROUND: European studies provide a preponderance of evidence for sublingual allergen immunotherapy (SLIT) safety and efficacy, but they use allergen products that differ from those expected to be approved in the United States. OBJECTIVE: To determine the safety and tolerability of 4 US-licensed standardized SLIT allergenic extracts. METHODS: Adults 18 to 50 years old with allergic rhinitis with or without asthma due to timothy grass pollen, short ragweed pollen, house dust mite, or cat hair allergy completed a single-session dose escalation followed by an 8-week, open-label daily course of SLIT. Participants documented the presence and severity of adverse effects and adherence using a daily electronic diary. RESULTS: Ninety-one participants initiated treatment, and 77 completed the phase 1 testing. Maximum tolerable doses ranged from 50 to 2,090 BAU for cat hair and dust mite extract, 31 to 91 Amb a 1 Units for short ragweed pollen extract, and 50 to 21,090 BAU for timothy grass pollen extract. During the 8-week treatment course, 98.9% of participants reported at least 1 mild, 70.4% at least 1 moderate, and 13.6% at least 1 severe adverse effect. Most adverse effects (94.6%) were rated as mild, 5.2% as moderate, and 0.1% as severe; nasal and oral-mucosal adverse effects were most commonly reported. No life-threatening adverse reactions occurred in more than 4,500 administered doses. CONCLUSIONS: Daily sublingual-oral dosing of standardized allergenic extracts at maximum tolerable doses was generally well tolerated. These results are a first step toward establishing the safety of US-licensed SLIT extracts when appropriately self-administered and monitored.

Fluticasone propionate protects against ozone-induced airway inflammation and modified immune cell activation markers in healthy volunteers.

BACKGROUND: Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O(3)-induced airway inflammation, but their effect on innate immune activation is unknown. OBJECTIVES: We used a human O(3) inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers. METHODS: Seventeen O(3)-responsive subjects [>10% increase in the percentage of polymorphonuclear leukocytes (PMNs) in sputum, PMNs per milligram vs. baseline sputum] received placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O(3) challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1-5 hr after the O(3) challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation. RESULTS: FP had no effect on O(3)-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O(3)-induced sputum neutrophilia by 18% and 35%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment significantly reduced O(3)-induced modification of CD11b, mCD14, CD64, CD16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner. CONCLUSIONS: This study confirmed and extended data demonstrating the protective effect of FP against O(3)-induced airway inflammation and immune cell activation.

In vivo gamma-tocopherol supplementation decreases systemic oxidative stress and cytokine responses of human monocytes in normal and asthmatic subjects.

We have recently reported that gamma-tocopherol (gammaT) reduces allergen- and zymosan-induced inflammation using rodent models. As an initial step in extending these observations to humans, we conducted an open-label, Phase I dosing study of two doses (one or two capsules daily for 1 week) of a gamma-tocopherol-rich preparation containing 623 mg of gamma-tocopherol, 61.1 mg of d-alpha-tocopherol, 11.1 mg of d-beta-tocopherol (11.1 mg), and 231 mg of d-sigma-tocopherol per capsule. Endpoints for this study include serum levels of 5-nitro-gamma-tocopherol, as a marker of oxidative stress, and changes in serum gamma-, alpha-, and delta-tocopherol and gamma-2'-carboxyethyl-6-hydroxychroman (CEHC) 6 and 24 h after the first dose and after 1 week of treatment. To assess the biological activity of this treatment, we obtained peripheral blood mononuclear cells at baseline and after 1 week of treatment with two capsules of a gamma-tocopherol-rich preparation/day and examined the inflammatory cytokine response of these cells in culture to ex vivo endotoxin/LPS (0.01 ng/ml) challenge. We also monitored a number of safety endpoints to examine how well this preparation is tolerated in eight normal volunteers (four allergic and four nonallergic) and eight allergic asthmatics. We further obtained human monocytes from a subset of these volunteers and treated them ex vivo with gammaT, alphaT, gamma-CEHC, and alpha-CEHC and assessed their actions on LPS-induced degradation of IkappaBalpha and JNK signaling and ROS generation. As detailed herein, this open-label study demonstrates that gamma-tocopherol-enriched supplementation decreased systemic oxidative stress, increased serum levels of gamma-tocopherol, and inhibited monocyte responses to LPS without any adverse health effects. Further, in vitro treatment of human monocytes with gamma-CEHC and alpha-CEHC inhibits ROS generation and LPS-induced degradation of IkappaB and JNK activation.

Ozone enhancement of lower airway allergic inflammation is prevented by gamma-tocopherol.

Ozone is a commonly encountered environmental oxidant which has been linked to asthma exacerbation in epidemiological studies. Ozone induces airway inflammation and enhances response to inhaled allergen. It has been suggested that antioxidant therapy may minimize the adverse effects of ozone in asthma. We have previously shown that the antioxidant gamma-tocopherol (gammaT), an isoform of vitamin E, also has anti-inflammatory effects. We employed a Brown Norway rat model of ozone-enhanced allergic responses to test the therapeutic effects of gammaT on O(3)-induced airway inflammation. Ovalbumin (OVA)-sensitized rats were intranasally challenged with 0 or 0.5% OVA on Days 1 and 2, and exposed to 0 or 1 ppm ozone (8 h/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg gammaT on Days 2 through 5. Pulmonary tissue and bronchoalveolar lavage fluid (BALF) were collected on Day 6. OVA challenge caused increased total cells (267% increase) and eosinophils (4000%) in BALF that was unaffected by ozone exposure. Morphometric evaluation of lung tissue revealed increases in intraepithelial mucosubstances (IM) (300%) and subepithelial eosinophils (400%) in main axial airways. Ozone exposure of allergic rats enhanced IM increases in proximal axial airways (200%), induced cys-leukotrienes, MCP-1, and IL-6 production in BALF, and upregulated expression of IL-5 and IL-13 mRNA. gammaT treatment had no effect on IM increases by allergen, but blocked enhancement by ozone. gammaT attenuated both OVA- or ozone-stimulated eosinophilic infiltration, and increases of BALF cys-leukotrienes, MCP-1, and IL-6, as well as IL-5 and IL-13 mRNA. These data demonstrate broad anti-inflammatory effects of a gammaT and suggest that it may be an effective therapy of allergic airway inflammation.