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 PGD2. Que and cromolyn also inhibit histamine, leukotrienes and PGD2 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.

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The allergen Dpt 4 from the house dust mite Dermatophagoides pteronyssinus was shown to be a lipoprotein as judged by its Sudan black B staining properties. Ultracentrifugal studies confirmed this finding and showed that Dpt 4 was polydisperse, although the majority of the allergen belonged to a very high density lipoprotein class. Physicochemical studies using gradient polyacrylamide gel electrophoresis showed that Dpt 4 had an apparent molecular weight of 244,000 daltons and a particle diameter of 10.73 nm. Agarose gel electrophoresis showed that the allergen had an electrophoretic mobility 0.86 times that of human α-lipoprotein. The observation that Dpt 4 is a lipoprotein is consistent with earlier studies which showed that the allergen was heterogeneous with regard to its molecular weight and that it contained the hapten phosphorylcholine.