Immunopharmacology of the atopic diseases.
The atopic conditions, atopic dermatitis, asthma, and allergic rhinitis, may arise as a result of infiltrating bone marrow-derived cells into skin or respiratory mucosae. Release of inflammatory factors from these cells could account for cutaneous vascular instability and pruritus in atopic dermatitis. Erythema and itch have been induced by experimental stress interviews and by blind food challenges. In the latter, increased plasma histamine was detected and correlated with cutaneous reactions. Basophils from patients with atopic dermatitis have increased histamine release after exposure to immunologic or nonimmunologic lectin stimuli. This increased releasability may relate to inadequate cyclic AMP regulation of cell function. We have found that leukocytes of patients with atopic dermatitis have elevated phosphodiesterase activity and consequently reduced intracellular cyclic AMP. Exposure of the cells to a phosphodiesterase inhibitor caused considerable reduction in histamine release. Similarly, exposure of atopic B lymphocytes to a phosphodiesterase inhibitor greatly reduced the high spontaneous IgE synthesis in mononuclear leukocyte cultures. Elevated leukocyte phosphodiesterase activity may also serve as a marker for the atopic diathesis. We have found elevated enzyme activity in umbilical cord blood from newborns with atopic parents, suggesting that this defect may relate to a genetically determined defect. These studies have provided insight into basic abnormalities associated with atopic dermatitis and the atopic diathesis. Defects of regulatory mechanisms in immune and inflammatory cells may help explain the seemingly disparate disorders of physiologic, pharmacologic, and immunologic systems in atopy.
J M
JM
Hanifin
J M
JM
Butler
S C
SC
Chan
D001249:Asthma / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects; D001491:Basophils / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D003876:Dermatitis, Atopic / Q000276:immunology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D066298:In Vitro Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*
D010726:Phosphodiesterase Inhibitors; D007073:Immunoglobulin E; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases