Endocrine Abstracts (2004) 7 OC20

Steroid modulation of peripheral cytokine expression: increased resistance to dexamethasone and progesterone inhibition of type 1 CD4+ response in autoimmune thyroiditis

OE Okosieme, LDKE Premawardhana, AB Parkes & JH Lazarus

Department of Medicine, University of Wales College of Medicine, Cardiff, UK.

Glucocorticoids may regulate the autoimmune response by influencing the shift in balance between type-1 and type-2 cytokine responses. To investigate the effect of steroids on peripheral cytokine expression in autoimmune thyroiditis we measured dexamethasone (Dex) and progesterone (Prg) inhibition of peripheral CD4+ T lymphocyte expressions of Interferon-gamma (IFN-g) (type-1 response) and Interleukin-4 (IL-4) (type 2 response) in both patients and healthy subjects.

Subjects were patients with Hashimoto's thyroiditis (n=8) and healthy controls (n=12). Peripheral blood mononuclear cells were isolated from whole blood by density-gradient centrifugation and stimulated with phorbolmyristate acetate (PMA) and ionomycin in the presence or absence of varying doses of Dex and Prg (10-8, 10-6, 10-4). Monensin was added to inhibit cytokine release. After fixation and permeabilisation, cells were stained with the appropriate antibodies and cytokine expression by CD4 + lymphocytes was determined by flow cytometry.

Results are in means plus/minusSD. We observed a higher IFN- g/IL-4 ratio in CD4+ cells of thyroiditis patients (11.91 plus/minus4.11) than in controls (4.21 plus/minus2.04). Percentage inhibition of CD4+IFN- g expression by Dex was higher in control subjects (26.74plus/minus7.04) than in patients (18.92plus/minus7.66); P<0.05. Likewise, inhibition of IFN- g expression by Prg was higher in control subjects (27.07plus/minus6.48) than in patients (18.06plus/minus7.72); P<0.05. However, for both control subjects and patients, Dex and Prg inhibition of CD4+IL-4 expression was insignificant.

This data suggest that steroid-induced inhibition of peripheral type-1 response differs for AITD patients and controls. The relative resistance to the inhibitory effects of steroids on cytokine expression in AITD may signal one possible mechanism towards the type-1 dominance of AITD.

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