Serotonergic mechanisms in atopic dermatitis

Sammanfattning: Atopic dermatitis (AD) may be worsened by stress and anxiety. Serotonin (5-hydroxytryptamine; 5-HT) is an important mediator in stress and anxiety. In the present thesis serotonergic mechanisms were studied in atopic dermatitis (AD). In an atopic-like mouse model, NC/Nga, that was subjected to chronic mild stress, we studied expression of serotonergic markers 5-HT1A and 5-HT2A receptors (R) and serotonin transporter protein (SERT) in skin, cerebrum and cerebellum. There was an upregulation of 5-HT1AR in the skin, cerebrum and cerebellum, during inflammation, irrespective of stress, while the 5-HT2AR was upregulated in the cerebrum, hippocampal CA1 area, and in the cerebellum, Purkinje cell layer, while being downregulated in the skin, during chronic mild stress. In human AD patients serotonergic markers in relation to extent of the disease, pruritus, chronic stress and psychodemographic data with focus on trait anxiety and depression, were studied. We found a correlation between the extent of the disease and dermal 5-HT1AR-positive dermal inflammatory cells in the lesional skin and 5-HT2AR-positive vessels in the non-lesional skin, respectively. There was a correlation between depression with the epidermal positive 5-HT1AR fraction, while a reverse correlation with the number of 5-HT2AR expressing vessels, both in the lesional skin. In the lesional skin there was a reverse correlation for the basal SERT immunoreac-tivity with stress susceptibility. Moreover, the effect of intradermal injection of 5-HT was studied in patients with AD and in healthy controls, on vascular response and pruritus, estimated by a computerized VAS recorder. No difference was seen regarding pruritus, while the vascular response to 5-HT was reduced in the AD patients, compared to the healthy controls.