Biomedical subjects

Erwin W Gelfand

Publications and source records attributed to Erwin W Gelfand.

At least 19 recordsLinked to original sources

PubMed2007

Critical role of the Fc receptor gamma-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation.

The FcR common gamma-chain (FcRgamma) is an essential component of the receptors FcepsilonRI, FcgammaRI, and FcgammaRIII, which are expressed on many inflammatory cell types. The role of these receptors in the initiation or maintenance of allergic inflammation has not been well defined. FcRgamma-deficient (FcRgamma(-/-)) and control (wild-type (WT)) mice were sensitized and subsequently challenged with OVA. Following sensitization and challenge to OVA, FcRgamma-deficient (FcRgamma(-/-)) mice developed comparable levels of IgE and IgG1 as WT mice. However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to inhaled methacholine. Reconstitution of FcRgamma(-/-) mice with whole spleen MNC from WT mice before sensitization restored development of AHR and the numbers of eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization but before OVA challenge only partially restored these responses. These responses were also restored when FcRgamma(-/-) mice received T cell-depleted MNC, T and B cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization from FcR(+/+) or FcgammaRIII-deficient but not FcRgamma(-/-) mice. The expression levels of FcgammaRIV on bone marrow-derived dendritic cells from FcR(+/+) mice were found to be low. These results demonstrate that expression of FcRgamma, most likely FcgammaRI, on APCs is important during the sensitization phase for the development of allergic airway inflammation and AHR.

Allergens↗

PubMed2006

Spontaneous airway hyperresponsiveness in estrogen receptor-alpha-deficient mice.

RATIONALE: Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans. OBJECTIVES: To examine the role of estrogen receptors in modulating lung function and airway responsiveness using estrogen receptor-deficient mice. METHODS: Lung function was assessed by a combination of whole-body barometric plethysmography, invasive measurement of airway resistance, and isometric force measurements in isolated bronchial rings. M2 muscarinic receptor expression was assessed by Western blotting, and function was assessed by electrical field stimulation of tracheas in the presence/absence of gallamine. Allergic airway disease was examined after ovalbumin sensitization and exposure. MEASUREMENTS AND MAIN RESULTS: Estrogen receptor-alpha knockout mice exhibit a variety of lung function abnormalities and have enhanced airway responsiveness to inhaled methacholine and serotonin under basal conditions. This is associated with reduced M2 muscarinic receptor expression and function in the lungs. Absence of estrogen receptor-alpha also leads to increased airway responsiveness without increased inflammation after allergen sensitization and challenge. CONCLUSIONS: These data suggest that estrogen receptor-alpha is a critical regulator of airway hyperresponsiveness in mice.

Acetylcholine↗

PubMed2006

IL-2 and IL-18 attenuation of airway hyperresponsiveness requires STAT4, IFN-gamma, and natural killer cells.

IL-18 is known to induce IFN-gamma production, which is enhanced when combined with IL-2. In the present study, we investigated whether the combination of exogenous IL-2 and IL-18 alters airway hyperresponsiveness (AHR) and airway inflammation. Sensitized mice exposed to ovalbumin (OVA) challenge developed AHR, inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and increases in levels of Th2 cytokines and goblet cell numbers. The combination of IL-2 and IL-18, but neither alone, prevented these changes while increasing levels of IL-12 and IFN-gamma. The combination of IL-2 and IL-18 was ineffective in IFN-gamma-deficient and signal transducer and activator of transcription (STAT)4-deficient mice. Flow cytometry analysis showed significant increases in numbers of IFN-gamma-positive natural killer (NK) cells in the lung after treatment with the combination therapy, and transfer of lung NK cells isolated from sensitized and challenged mice treated with the combination significantly suppressed AHR and BAL eosinophilia. These data demonstrate that the combination of IL-2 and IL-18 prevents AHR and airway inflammation, likely through IL-12-mediated induction of IFN-gamma production in NK cells.

Adoptive Transfer↗

PubMed2006

IL-13 is essential to the late-phase response in allergic rhinitis.

BACKGROUND: The pathophysiology of the early- and late-phase nasal response to allergen challenge is not completely defined. Recent technical advances enable direct monitoring of these responses in mice. OBJECTIVE: IL-13 is detected in the nasal membranes of both human beings and mice with allergic rhinitis, but its role in disease pathogenesis is unclear. We measured early and late nasal allergic responses after treatment with soluble IL-13Ralpha2-IgG fusion protein (sIL-13Ralpha2-Fc), and in IL-13-deficient mice (IL-13(-/-)). METHODS: IL-13(-/-) mice (BALB/c background) and wild-type mice were sensitized to ovalbumin by intraperitoneal injection and then challenged intranasally with ovalbumin without sedation. The sIL-13Ralpha2-Fc or control human IgG was administered by intraperitoneal (i.p.) injection 24 hours and 1 hour before each ovalbumin challenge. Early nasal responses after the 4th ovalbumin challenge and late nasal responses 24 hours after the 6th ovalbumin challenge were assessed. RESULTS: Sensitized/challenged wild-type mice treated with sIL-13Ralpha2-Fc or IL-13(-/-) mice demonstrated significantly reduced late nasal responses in face of persistent nasal tissue eosinophilia; the early nasal response was little affected by targeting IL-13. Goblet cell hyperplasia was not detected in nasal membranes. CONCLUSION: The data indicate that IL-13 is a major contributor to the development of a late nasal response with little influence on the early response, and without affecting nasal eosinophilic inflammation. Inhibition of IL-13 may have an important therapeutic application in preventing the persistent nasal blockage in allergic rhinitis. CLINICAL IMPLICATIONS: Current therapies for allergic rhinitis may not take into account the important differences in the pathophysiology of the early and late responses and the important role of IL-13 in sustaining chronic nasal congestion and obstruction.

Animals↗

PubMed2006

Urine leukotriene E4 levels are associated with decreased pulmonary function in children with persistent airway obstruction.

BACKGROUND: Use of leukotriene receptor antagonists improves disease control in children and adults with asthma. However, the relationship between cysteinyl leukotriene levels and indices of daily asthma control has not been studied directly. OBJECTIVES: We sought to assess the relationship between daily variability in urinary leukotriene E(4) (LTE(4)) levels and daily lung function in children primarily taking inhaled corticosteroids (ICSs) and long-acting beta-agonists (LABAs). METHODS: Fifty children primarily with moderate-to-severe asthma were followed with measurements of urinary LTE(4), monitoring of FEV(1), and albuterol use. RESULTS: Increasing urinary LTE(4) levels were associated with significant (P = .006) decreases in percent predicted FEV(1) (ppFEV(1)) averaging 4.7% per interquartile range increase in LTE(4) and accompanied by increased albuterol use (P = .03). Children with lower FEV(1)/forced vital capacity ratios demonstrated larger LTE(4)-related FEV(1) decreases (6.4%) compared to those with higher ratios (4.2%, P = .009). This association was blunted in children taking montelukast (1.4% ppFEV(1) decrease) compared with that in children not taking this medication (5.4% ppFEV(1) decrease, P = .05). Children with lower lung function ratios demonstrated greater blunting of the LTE(4) effect with montelukast (0.9% ppFEV(1) decrease) compared to those with higher ratios (3.6% ppFEV(1), P = .0002). CONCLUSIONS: Daily variability in LTE(4) levels is associated with clinically significant decreases in pulmonary function. In children who demonstrate a response associated with an increase in urinary LTE(4) levels, leukotriene receptor antagonists protect against daily FEV(1) decreases. This protection might be greatest in those with persistent airway obstruction despite use of ICS and LABA therapy. CLINICAL IMPLICATIONS: Therapies designed to block cysteinyl leukotriene production or function might benefit children receiving ICS and LABA therapy who continue to experience persistent disease.

Acetates↗

PubMed2006

Safety and tolerability of increased rate of infusion of intravenous immunoglobulin G, 10% in antibody-deficient patients.

The incidence and severity of infusion-related adverse events (AEs) after infusions of IGIV-C, 10%, (Gamunex) at 0.14 mL/kg/min versus 0.08 mL/kg/min (standard rate) were compared. Patients with confirmed PID received two infusions 3-4 weeks apart with IGIV-C, 10% 400-600 mg/kg. Patients received their first infusion at 0.08 or 0.14 mL/kg/min and their second infusion 3-4 weeks later at the alternate rate, at an established step-wise rate increase. Ninety-seven of 100 patients remained valid for safety assessment. There were three infusion-related reactions at the standard rate and five at the increased rate. The incidence of all reported AEs was similar for both rates. Despite the time required for step-wise increases in infusion rate, the increased rate resulted in a shortened overall infusion time. Increasing the rate of infusion of IGIV-C, 10% by 75% up to 0.14 mL/kg/min (840 mg/kg/h) was well tolerated, suggesting safe administration of IGIV-C, 10% at this rate.

Adolescent↗

PubMed2006

Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation.

Exposure to inhaled allergens leads to increases in airway hyperresponsiveness (AHR) and inflammation, associated with increased levels of biologically active fragments derived from the complement C3 and C5 family of proteins. Further, complement activation during allergen challenge in sensitized animals is necessary for the development of AHR and airway inflammation. To define the complement pathway involved, we studied mice deficient in complement factor 4 (C4-/-), a critical component of the classical pathway, or factor B (fB-/-), an essential protein in the alternative complement pathway. WT, C4-/-, and fB-/- mice were sensitized to ovalbumin and subsequently exposed to nebulized ovalbumin (1% in saline) on 3 consecutive days. After allergen sensitization and challenge, fB-/- mice demonstrated significantly lower airway responsiveness to methacholine and less airway inflammation. In contrast, C4-/- mice showed no reduction in AHR and airway inflammation compared with WT mice. Tissue inflammation, goblet cell hyperplasia, and IL-4, IL-5, and IL-13 levels in BAL fluid were significantly reduced in fB-/- mice compared with C4-/- and WT mice. The development of AHR and airway inflammation in sensitized fB-/- mice could be restored after intranasal administration of purified factor B before the airway challenge. In addition, administration of a neutralizing anti-factor B mAb to sensitized mice before airway challenge reduced the development of AHR and airway inflammation. These results demonstrate that in sensitized hosts complement activation through the alternative pathway after allergen exposure is critical to the development of AHR and airway inflammation.

Animals↗

PubMed2006

Pirfenidone modulates airway responsiveness, inflammation, and remodeling after repeated challenge.

We investigated the therapeutic potential of a newly developed antifibrotic agent, pirfenidone, to regulate airway remodeling and the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenge. Administration of pirfenidone after sensitization but during the period of ovalbumin challenge significantly prevented the development of airway hyperresponsiveness and prevented eosinophil and lymphocyte accumulation in the airways. IL-4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid and ovalbumin-specific serum IgE antibody levels were also significantly reduced. Treatment with pirfenidone significantly reduced transforming growth factor-beta1 and platelet-derived growth factor levels in bronchoalveolar lavage fluid. Pirfenidone reduced the expression of transforming growth factor-beta1, the development of goblet cell hyperplasia and subepithelial collagenization, and the increases in contractile elements in the lung. These data indicate that pirfenidone may play an important role in the treatment of asthma and has the potential reduce or prevent airway remodeling.

Allergens↗

PubMed2006

RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge.

RANTES (CC chemokine ligand 5) contributes to airway inflammation through accumulation of eosinophils, but the exact role of RANTES (CCL5) is not defined. C57BL/6 mice, sensitized by injection of ovalbumin (OVA) on Days 1 and 14, were challenged with OVA on Days 28, 29, and 30 (3 challenges, short-term-challenge model) or on Days 28, 29, 30, 36, 40, 44, and 48 (7 challenges, repeated-challenge model) and evaluated 48 h later. Anti-mouse RANTES was given intravenously, and recombinant mouse RANTES or PBS was given intratracheally. These reagents were given on Days 28, 29, and 30 in the short-term-challenge study and on Days 44 and 48 in the repeated-challenge study. After short-term challenge, there were no effects after administration of anti-RANTES or RANTES. In the repeated-challenge study, although control mice showed a decrease in airway hyperresponsiveness, administration of anti-RANTES sustained and enhanced airway hyperresponsiveness and increased goblet cell numbers. In contrast, administration of RANTES normalized airway function but reduced goblet cell numbers. IL-12 and IFN-gamma levels in BAL decreased in the anti-RANTES group and increased in the RANTES group. IFN-gamma-producing CD4 T cells in lung, and IFN-gamma production from lung T cells in response to OVA in the anti-RANTES group, were significantly decreased but were increased in the RANTES group. Anti-IFN-gamma, administered with RANTES, decreased the effects of RANTES on AHR after repeated challenge. These data indicate that RANTES plays a role in the regulation of airway function after repeated allergen challenge, in part through modulation of levels of IFN-gamma and IL-12.

Allergens↗

PubMed2006

The leukotriene B4 receptor (BLT1) is required for effector CD8+ T cell-mediated, mast cell-dependent airway hyperresponsiveness.

Studies in both humans and rodents have suggested that CD8+ T cells contribute to the development of airway hyperresponsiveness (AHR) and that leukotriene B4 (LTB4) is involved in the chemotaxis of effector CD8+ T cells (T(EFF)) to the lung by virtue of their expression of BLT1, the receptor for LTB4. In the present study, we used a mast cell-CD8-dependent model of AHR to further define the role of BLT1 in CD8+ T cell-mediated AHR. C57BL/6+/+ and CD8-deficient (CD8-/-) mice were passively sensitized with anti-OVA IgE and exposed to OVA via the airways. Following passive sensitization and allergen exposure, C57BL/6+/+ mice developed altered airway function, whereas passively sensitized and allergen-exposed CD8-/- mice failed to do so. CD8-/- mice reconstituted with CD8+ T(EFF) developed AHR in response to challenge. In contrast, CD8-/- mice reconstituted with BLT1-deficient effector CD8+ T cells did not develop AHR. The induction of increased airway responsiveness following transfer of CD8+ T(EFF) or in wild-type mice could be blocked by administration of an LTB4 receptor antagonist confirming the role of BLT1 in CD8+ T cell-mediated AHR. Together, these data define the important role for mast cells and the LTB4-BLT1 pathway in the development of CD8+ T cell-mediated allergic responses in the lung.

Adoptive Transfer↗

PubMed2006

Particulate levels are associated with early asthma worsening in children with persistent disease.

RATIONALE: Ambient particulate concentrations have been associated with variable physiologic effects in children with persistent asthma taking controller medications. OBJECTIVE: To determine whether exposure to particulate matter has immediate effects on asthma control in children with persistent disease. METHODS AND MEASUREMENTS: In a school-based cohort, 73 children, primarily with moderate and severe asthma, were followed daily over one or two winters (2001-2002, 2002-2003) in Denver, Colorado. The association among ambient fine particulate, bronchodilator use, and urinary leukotriene E4 levels was assessed. RESULTS: Daily concentrations of fine particulate peaked in the morning hours when children were commuting to school. In a multivariable analysis that controlled for meteorology, time trends, and upper respiratory infections, an increase of one interquartile range in morning maximum fine particulate levels was related to an average increase of 3.8% in bronchodilator usage at school (95% confidence interval [CI], 0.2-7.4; p = 0.04). Children with severe asthma demonstrated significantly stronger associations (8.1% increase; 95% CI, 2.9-13.4; p = 0.003) than those with mild/moderate disease (1.6% increase; 95% CI, -2.2-5.4; p = 0.41; p = 0.03 for difference between groups). Morning maximum fine particulate levels were also associated with urinary leukotriene E4 measured during school hours (average increase of 6.2% per interquartile range increase; 95% CI, 1.9-10.5; p = 0.006). These associations were not discernable when 24-h averaged concentrations were used. CONCLUSIONS: Peak concentrations of ambient fine particulate are associated with early increases in bronchodilator use and urinary leukotriene E4 levels among children with persistent asthma, despite the use of controller medications.

Adolescent↗

PubMed2006

Protein kinase C alpha, betaI, and betaII isozymes regulate cytokine production in mast cells through MEKK2/ERK5-dependent and -independent pathways.

Regulation of MAPK pathways by PKC isoforms was examined in murine bone marrow-derived mast cells (BMMCs). The PKCalpha, betaI, and betaII isoforms showed the most robust activation after FcepsilonR1-mediated stimulation by anti-ovalbumin specific IgE and ovalbumin (IgE-ova). PKCalpha, betaI, and betaII were all involved in activation of JNK, MEKK2, and ERK5, with differential relative contributions of each isoform to specific MAPK pathway components. BMMCs from mice lacking MEKK2 showed reduced production (50-60%) of IL-6, IL-13, and TNF-alpha after stimulation, demonstrating MEKK2-dependent and -independent pathways for cytokine production. Cytokine production was stimulated by over-expression of PKC in cells from MEKK2-deficient and wild-type mice. Activation of ERK5 did not occur in BMMCs lacking MEKK2, indicating that MEKK2-independent cytokine production was also ERK5-independent. Since MAPK modules differentially regulate mast cell functions, including degranulation and cytokine production, it is suggested that specific functions could be targeted by inhibiting specific PKC isoforms.

Animals↗

PubMed2006

CD8+ T lymphocytes and leukotriene B4: novel interactions in the persistence and progression of asthma.

The contribution of CD8+ T cells to the development of airway hyperresponsiveness and airway inflammation has received increased attention recently. CD8+ T cells, which are capable of secreting TH2 cytokines, including IL-4, IL-5, and IL-13, have been described in asthmatic subjects and in animals sensitized and challenged with allergen. A subset of these IL-13-producing CD8+ T cells, effector memory CD8+ T cells in the mouse, express a high-affinity receptor for leukotriene B4 (BLT1), and expression of this receptor is essential for their accumulation in the lung and development of airway hyperresponsiveness and airway inflammation. A similar subset of CD8+/BLT1+/IL-13+ T cells has also been identified in the bronchoalveolar lavage fluid of asthmatic subjects, suggesting a pathogenic role for this unique subset of CD8+ T cells in asthma.

Animals↗

PubMed2006

Once-daily ciclesonide in children: efficacy and safety in asthma.

OBJECTIVE: To compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug (CIC40), 80 mug (CIC80), and 160 mug (CIC160) with placebo in children with persistent asthma of all severities. STUDY DESIGN: Overall, 1031 children age 4 to 11 years were randomized into 2 identical double-blinded, placebo-controlled, parallel group studies consisting of a run-in phase followed by 12 weeks of treatment. Both studies were designed to allow for a prespecified integrated analysis. The primary outcome variable was change in forced expiratory volume in 1 second (FEV(1)) percent predicted between baseline and study end; treatment comparisons were assessed using analysis of covariance. Additional endpoints included asthma symptom scores, daily albuterol use, and safety, including hypothalamic-pituitary-adrenal (HPA) axis function. RESULTS: Baseline characteristics were comparable; 59.4% of patients had moderate asthma, and 24.1% had severe asthma. All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1) percent predicted versus placebo (CIC40, 11.97; CIC80, 13.58, P <.05; CIC160, 14.17, P < .01). Significant improvements in asthma symptoms (P < .01) and reductions in albuterol use were reported. Ciclesonide was well tolerated with no effect on HPA axis function. CONCLUSIONS: In this integrated analysis, ciclesonide was effective and well tolerated in children with persistent asthma.

Adrenal Cortex Hormones↗

PubMed2006

Use of the health plan employer data and information set for measuring and improving the quality of asthma care.

OBJECTIVES: To discuss the Health Plan Employer Data and Information Set (HEDIS) criteria for measuring performance in asthma care and to review new strategies to improve the quality of asthma care. DATA SOURCES: Expert opinion from a roundtable on National Committee for Quality Assurance HEDIS and asthma care, supplemented with a MEDLINE database search to identify articles published between January 1, 1990, and May 31, 2005, with the following keywords in the title: asthma plus HEDIS, pay for performance, incentive programs, reimbursement, or employee education. STUDY SELECTION: Studies and review articles were selected for their relevance to measuring the quality of asthma care using HEDIS and improving care using newer trends, such as employee education and physician incentive programs. RESULTS: Components of the HEDIS asthma measure have been found to correlate with outcomes, including risk of hospitalization and emergency department visits. However, refinements to the measure may be needed because it may misclassify a portion of patients as having persistent asthma who actually have intermittent asthma according to National Heart, Lung, and Blood Institute criteria. Physician incentive programs are increasingly being explored as a means of improving the quality of care while managing costs. Under current pay-for-performance programs, rewards are issued to providers who demonstrate high-quality care based on the HEDIS asthma measure. CONCLUSIONS: The HEDIS asthma measure remains the most widely used performance tool for evaluating the quality of asthma care. Reimbursement models based on public reporting and pay for performance are expected to be a strong component of future health care payment systems.

Adolescent↗

PubMed2006

Effect of montelukast on peripheral airflow obstruction in children with asthma.

BACKGROUND: Montelukast is a widely used controller agent in childhood asthma. It is modestly effective in reducing symptoms, decreasing the need for rescue albuterol, and improving forced expiratory volume in 1 second (FEV1). OBJECTIVE: To determine whether montelukast therapy improves peripheral airway obstruction as measured by lung volumes, air trapping, airway resistance (Raw), and specific conductance (Sgaw). METHODS: Twenty-one children aged 9 to 18 years with mild-to-moderate asthma were randomized into a double-blind, placebo-controlled study to receive montelukast (5 or 10 mg) or matching placebo daily for 8 weeks. Symptoms and albuterol use were recorded twice daily, and exhaled nitric oxide measurement, forced oscillometry, spirometry, and body box plethysmography (before and after beta-agonist use) were performed at randomization and at 2, 4, 6, and 8 weeks. Circulating eosinophil counts and serum eosinophil cationic protein (ECP) levels were obtained at randomization and at 8 weeks. RESULTS: Montelukast-treated patients had lower residual volume (P = .05), residual volume-total lung capacity ratio (P = .04), Raw (P = .02), Sgaw (P = .03), and serum ECP levels (P = .02) at 8 weeks compared with those treated with placebo. There was a trend toward reduced daytime and nighttime albuterol use, although the difference did not reach statistical significance. There were no significant differences in FEV1, FEV1-forced vital capacity ratio, exhaled nitric oxide levels, or daytime and nighttime symptom scores between the 2 groups. CONCLUSIONS: Montelukast therapy was associated with less air trapping, hyperinflation, and Raw and better Sgaw compared with placebo. Lower serum ECP levels, a surrogate measure of airway inflammation, were associated with improvements in lung function.

Acetates↗

PubMed2006

Estimating effects of ambient PM(2.5) exposure on health using PM(2.5) component measurements and regression calibration.

Most air pollution and health studies conducted in recent years have examined how a health outcome is related to pollution concentrations from a fixed outdoor monitor. The pollutant effect estimate in the health model used indicates how ambient pollution concentrations are associated with the health outcome, but not how actual exposure to ambient pollution is related to health. In this article, we propose a method of estimating personal exposures to ambient PM(2.5) (particulate matter less than 2.5 microm in diameter) using sulfate, a component of PM(2.5) that is derived primarily from ambient sources. We demonstrate how to use regression calibration in conjunction with these derived values to estimate the effects of personal ambient PM(2.5) exposure on a continuous health outcome, forced expiratory volume in 1 s (FEV(1)), using repeated measures data. Through simulation, we show that a confidence interval (CI) for the calibrated estimator based on large sample theory methods has an appropriate coverage rate. In an application using data from our health study involving children with moderate to severe asthma, we found that a 10 microg/m3 increase in PM(2.5) was associated with a 2.2% decrease in FEV(1) at a 1-day lag of the pollutant (95% CI: 0.0-4.3% decrease). Regressing FEV(1) directly on ambient PM(2.5) concentrations from a fixed monitor yielded a much weaker estimate of 1.0% (95% CI: 0.0-2.0% decrease). Relatively small amounts of personal monitor data were needed to calibrate the estimate based on fixed outdoor concentrations.

Air Pollutants↗

PubMed2006

Role of the LTB4/BLT1 pathway in allergen-induced airway hyperresponsiveness and inflammation.

LTB4, a proinflammatory lipid mediator generated from arachidonic acid through the action of 5-lipoxygenase, has been known for over two decades and is implicated in a wide variety of inflammatory disorders. BLT1, a G-protein-coupled receptor, has recently been identified as a high affinity receptor specific for LTB4. Recent studies in allergen-induced airway hyperresponsiveness and inflammation using mice lacking BLT1 have shown crucial new roles for leukotriene B4 and BLT1 in Th2 cytokine IL-13 production from lung T cells and recruitment of antigen-specific effector CD8+ T cells, suggesting novel mechanisms for their actions. The leukotriene B4-BLT1 pathway is an important target for the treatment of bronchial asthma.

Allergens↗