title: Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
abstract: Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell "stabilizer", is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine, leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Zuyi
authors.initials: Z
authors.lastname: Weng
authors.forename: Bodi
authors.initials: B
authors.lastname: Zhang
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Asadi
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Sismanopoulos
authors.forename: Alan
authors.initials: A
authors.lastname: Butcher
authors.forename: Xueyan
authors.initials: X
authors.lastname: Fu
authors.forename: Alexandra
authors.initials: A
authors.lastname: Katsarou-Katsari
authors.forename: Christina
authors.initials: C
authors.lastname: Antoniou
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004205:Cromolyn Sodium / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000276:immunology*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D015850:Interleukin-6; D016209:Interleukin-8 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D015230:Prostaglandin D2 / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D015850:Interleukin-6; D016209:Interleukin-8; D015289:Leukotrienes; D016328:NF-kappa B; C026408:anti-IgE antibodies; D007073:Immunoglobulin E; D006632:Histamine; D011794:Quercetin; D004205:Cromolyn Sodium; D015230:Prostaglandin D2; D002118:Calcium