cyclic-gmp and Dermatitis--Atopic

A summarizing survey of different studies in atopic eczema involving three types of cells (platelets, neutrophils, basophils) and their mediators is given. Platelets were found to release normal amounts of serotonin upon stimulation with epinephrine, thrombin and slightly reduced amounts after aggregated IgG stimulation. Serotonin uptake by washed platelets was found to be slower in atopics than in normals. Neutrophils showed a decreased release of beta-glucuronidase to stimuli like zymosan or aggregated IgG in atopics compared to controls. This might be regarded as a contributory factor to the well-known decreased resistance to infections observed in atopic eczema. Basophils in most studies released increased amounts of histamine in the atopic population compared to controls, especially after stimulation with anti-IgE. Concomitantly to the histamine release there was a slight increase in prostaglandin E2 production both in atopics and normals, which was increased by preincubation with reduced glutathion-a coenzyme of PGE2 isomerase. Histamine release tended to occur faster in atopics. Two possible factors influencing releasability characteristics were studied, namely the cyclic nucleotide system and arachidonic acid (AA) dependent mechanisms. Leucocytes of atopics showed a decreased response of cAMP to beta-adrenergic and an increased response of cGMP to cholinergic stimulation. Significant augmentation of anti-IgE-induced histamine release was observed after cholinergic stimulation. AA metabolites obviously play a regulating role in mediator release. PGE2 inhibited histamine release to various stimuli both in atopics and in normals. Indomethacin enhanced histamine release, especially after anti-IgE stimulation in atopics, while it inhibited complement-dependent release reactions both in atopics and in normals. The exogenous inhibitors of lipoxygenase eicosatetraynoic acid (ETYA) and nordihydroguaretic acid (NDGA) inhibited histamine release equally in atopics and normals. The endogenous lipoxygenase inhibitor 15-HETE showed no inhibitory but rather a slight enhancing effect upon histamine release. It is concluded that patients with atopic eczema often exhibit altered releasability patterns to a variety of stimuli. On the basis of our findings we describe "altered releasability" as one factor of a vicious cycle between increased IgE-production, mediator secretion and T cell regulatory disturbances in the pathogenesis of atopic eczema.

Topics: Animals; Arachidonic Acids; Basophils; Blood Platelets; Complement Activation; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Glucuronidase; Histamine; Histamine Release; Humans; Immunoglobulin E; Indomethacin; Infant, Newborn; Neutrophils; Serotonin; Skin; Stimulation, Chemical; T-Lymphocytes

Topics: Adenylyl Cyclases; Adult; Asthma; Calcium; Child; Cromolyn Sodium; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Humans; Hypersensitivity; Immunoglobulin E; Muscle, Smooth; Phosphodiesterase Inhibitors

Topics: Affective Symptoms; Animals; Asthma; Caffeine; Calcitonin; Calcium; Catecholamines; Circadian Rhythm; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Diabetes Insipidus; Glucagon; Growth Hormone; Humans; Hypercalcemia; Hyperparathyroidism; Hypocalcemia; Hypoparathyroidism; Insulin; Organ Specificity; Parathyroid Hormone; Psoriasis; Vasopressins

Plasma cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) taken at distinct times of the day were measured in 45 inpatients with generalized atopic eczema (AE). The results were compared with 34 healthy controls. Female patients not taking oral contraceptives (OC) and male patients revealed significantly higher median levels of cAMP in comparison with the controls (p less than 0.002 for males; p less than 0.001 for females). No significant cAMP differences were found between patients of either sex and female controls taking OC. The median cGMP plasma levels did not differ between patients and controls. Both cyclic nucleotides are discussed under the aspect of cAMP as a second messenger of various hormones, reflecting and integrating different responses of the body to AE as a distressing systemic skin disorder.

Topics: Acute Disease; Adolescent; Adult; Circadian Rhythm; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Female; Humans; Male; Middle Aged

Peripheral blood leukocytes from patients with severe atopic dermatitis (serum IgE levels between 1,560 and 28,000 U/ml) showed a significantly weaker increase in intracellular cAMP after stimulation with epinephrine (10(-5)-10(-3) M) than leukocytes from normals. At the same time stimulation with methylcholine (10(-10)-(10(-4) M) induced a significantly higher increase in intracellular levels of cGMP in the atopic group compared to normals. The immunomodulating agent levamisole induced a slight increase in cAMP and cGMP response both in leukocytes from atopic patients and in normals. Platelet cAMP concentrations were lowered by epinephrine stimulation both in atopics and controls. There was no effect of methylcholine upon platelet cyclic nucleotide levels in the dose range examined. The data support the concept that abnormal cyclic nucleotide responsiveness--not only as beta-adrenergic blockade but also as cholinergic hyperreactivity--may plays a role in the pathogenesis of atopic dermatitis.

Topics: Adult; Blood Platelets; Choline; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Epinephrine; Female; Humans; Leukocytes; Levamisole; Male; Middle Aged; Nucleotides, Cyclic