Atopic Dermatitis: A Disease of General Vasoactive Mediator Dysregulation

Abstract

A simple hypothesis trying to explain the complex etiology of atopic dermatitis is presented. Based on the facts of various known immunologic and autonomic nervous system abnormalities the possible role of vasoactive mediators in this disease is stressed. There are several factors which favour a continuous tendency to release vasoactive substances, as for example histamine; the immunologically, IgE-mediated histamine release is only one of them. Basophils of atopic individuals show increased ‘releasability’ after stimulation with a variety of non-immunologic stimuli. Together with this increased releasability, a deficiency in control systems, as in the cyclic AMP-dependent mechanisms, is known, also favouring increased histamine release. Histamine as one of the mediators not only acts upon the capillaries, the bronchial and circulatory system, but on lymphocytes too: it is known that especially T cell functions can be inhibited by histamine in vitro and in vivo. Suppressor T cells are particularly sensitive to histamine being most likely the population of T lymphocytes bearing histamine receptors. In atopic dermatitis a specifically increased sensitivity of T cells to histamine has been described. Therefore, increased levels of histamine could explain the well-known cell-mediated immune deficiency in patients with atopic dermatitis as well as possibly their increased tendency to produce IgE antibodies. The latter hypothesis is based on animal experiments which clearly show that IgE production is favoured by a deficiency in the suppressor T cell system. This hypothesis puts together the most important pathological findings in this disease; a genetic defect as basis of ‘leaky’ mast cells and basophils seems likely.

Plasma histamine concentrations in atopic eczema

“…1977;Schopf, 1974). Therefore, increased levels of histamine-or other similar mediators-in blood and tissues might help explain the weakness of cell-mediated immune functions in these patients (Ring. 1979).…”

In vitro Cyclic Nucleotide Responsiveness of Leukocytes and Platelets in Patients Suffering from Atopic Dermatitis

“…Indeed, in creased amounts of histamine have been found to be released in vitro [28,30] and measured in the plasma of severely atopic patients [9,29,34]. In our study we ob served no significant correlation between the intensity of the clinical symptoms of dermatitis nor serum IgE concentration to the amount of change in intracellular cyclic nucleotides.…”

“…The well-known cellular immune defects in atopic dermatitis [25,33,42] might partly be explained by continuous histamine re lease [30].…”

Beta-2-Adrenoceptors of Polymorphonuclear Leukocytes in Children with Atopic Dermatitis

“…Szentivanyi [13,14] postulated an a-directed shift of the p2-adrenoceptors as the putative basic defect in AD. A decrease in the number or quality of the p2-adrenoceptors could account for the increase in liber ation of mediators of allergic reactivity from mast cells and basophil granulocyes as observed in atopic diseases [15]. Consequently, several investigators studied p2-adrenoceptors on peripheral leukocytes from patients with AD.…”