The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Feb 2013
Randomized Controlled Trial Multicenter StudySafety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients.
The D-prostanoid receptor and the chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) are implicated in asthma pathogenesis. AMG 853 is a potent, selective, orally bioavailable, small-molecule dual antagonist of human D-prostanoid and CRTH2. ⋯ AMG 853 as an add-on to inhaled corticosteroid therapy demonstrated no associated risks but was not effective at improving asthma symptoms or lung function in patients with inadequately controlled moderate-to-severe asthma.
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This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Atopic dermatitis: a practice parameter update 2012." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. ⋯ Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. Published practice parameters of the Joint Task Force on Practice Parameters for Allergy & Immunology are available online at http://www.jcaai.org.
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J. Allergy Clin. Immunol. · Feb 2013
Mast cell anaphylatoxin receptor expression can enhance IgE-dependent skin inflammation in mice.
Mast cells express receptors for complement anaphylatoxins C3a and C5a (ie, C3a receptor [C3aR] and C5a receptor [C5aR]), and C3a and C5a are generated during various IgE-dependent immediate hypersensitivity reactions in vivo. However, it is not clear to what extent mast cell expression of C3aR or C5aR influences C3a- or C5a-induced cutaneous responses or IgE-dependent mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo. ⋯ Expression of C3aR and C5aR by skin mast cells contributes importantly to the ability of C3a and C5a to induce skin swelling and can enhance mast cell degranulation and inflammation during IgE-dependent PCA in vivo.
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J. Allergy Clin. Immunol. · Feb 2013
A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent murine model of allergic asthma.
Sphingosine-1-phosphate (S1P), which is produced by 2 sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2, has been implicated in IgE-mediated mast cell responses. However, studies of allergic inflammation in isotype-specific SphK knockout mice have not clarified their contribution, and the role that S1P plays in vivo in a mast cell- and IgE-dependent murine model of allergic asthma has not yet been examined. ⋯ S1P and SphK1 play important roles in mast cell-dependent, OVA-induced allergic inflammation and AHR, in part by regulating the NF-κB pathway.
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J. Allergy Clin. Immunol. · Feb 2013
Spleen tyrosine kinase inhibition attenuates airway hyperresponsiveness and pollution-induced enhanced airway response in a chronic mouse model of asthma.
Asthma is a chronic inflammatory disease characterized by airways hyperresponsiveness (AHR), reversible airflow obstruction, airway remodeling, and episodic exacerbations caused by air pollutants, such as particulate matter (PM; PM <2.5 μm in diameter [PM(2.5)]) and ozone (O(3)). Spleen tyrosine kinase (Syk), an immunoregulatory kinase, has been implicated in the pathogenesis of asthma. ⋯ NVP-QAB-205 reduced AHR and the enhanced response to PM(2.5) plus O(3) to normal levels in an established model of chronic allergic airways inflammation, suggesting that Syk inhibitors have promise as a therapy for asthma.