Elevated Glucocorticoid Receptor Concentrations before and after Glucocorticoid Therapy in Peripheral Mononuclear Leukocytes of Patients with Atopic Dermatitis

Abstract

The number and affinity of glucocorticoid binding sites in peripheral mononuclear leukocytes of patients with atopic dermatitis (AD) and healthy controls were determined under baseline conditions and after a defined oral glucocorticoid treatment. Patients with AD (n = 15) exhibited significantly more glucocorticoid receptors (GR) per cell than the control group (n = 22), while the GR affinity did not differ. Methylprednisolone treatment resulted in a significant reduction of the GR sites per cell in the steroid-treated control group (n = 10) in contrast to the patients. The dissociation constant was not affected by methylprednisolone treatment in either group. In view of the therapeutic efficiency of glucocorticoids in AD and findings of abnormal cAMP and cAMP-phosphodiesterase activity, the elevated GR concentrations in AD lend support to the hypothesis of a compensatory GR upregulation due to an insufficient action of endogenous cortisol or to altered cAMP-induced GR expression.

In vivo and in vitro effects of glucocorticoids on lectin-induced blastogenesis in atopic dermatitis

“…Our data show a lowered suppression of some proliferation parameters of mononuclear leucocytes after in vivo administration of methylprednisolone, while the in vitro effects of dexamethasone appear to be normal. These findings together with recently reported alterations in glucocorticoid receptor pharmacology in AD [27] suggest a decreased biological efficiency of methylprednisolone on lymphocytes in vivo, the origin of which remains to be elucidated.…”

Psychoneuroimmunology of Psychological Stress and Atopic Dermatitis: Pathophysiologic and Therapeutic Updates

“…Atopic patients, including those with AD, respond to stress with suboptimal cortisol production (77–79). In accordance with that, atopic patients with seasonal allergic rhinitis showed attenuated cortisol responses to a standardized laboratory stressor test (Trier Social Stress Test) during an acute pollen season, but not during a pollen-free season (80).…”

Psikonöroimmünoloji ve Multifaktöryel Psikodermatolojik Hastalıklar

“…Atopik dermatitin Th2 hastal›k mekanizmas›n›n tipik bir örne¤i oldu¤u söylenebilir. Atopik bireylerin periferik lökositleri üzerindeki glukokortikoid reseptörleri stres kortizolüne afl›r› reaksiyon gösterecek potansiyele sahiptir ve böylece Th2 yönündeki kay›fl klinikte stres sonucu alevlenen dermatitin akut dönemi ile uyumlu karakteristik bulgular› sergiler 24 . Ek olarak stres glukokortikoidleri deri bariyerini de bozarak ev tozlar›, virüs, bakteri gibi çeflitli allerjenlerin ve patolojik uyar›-lar›n deriye girmesine ve dermatiti bafllatmas›na neden olur.…”

“…Ek olarak stres glukokortikoidleri deri bariyerini de bozarak ev tozlar›, virüs, bakteri gibi çeflitli allerjenlerin ve patolojik uyar›-lar›n deriye girmesine ve dermatiti bafllatmas›na neden olur. Sempatik kateflolaminler, nöropeptitler (SP,CGRP,VIP) ve nö-rotrofinlerin bölgesel ve lokal etkilerinin kat›l›m›yla emosyonel strese yan›t olarak geliflen kafl›nt› ve akut dermatit tablosu gerçekleflir [23][24][25][26][27] .…”