Peripheral cytokine expression in autoimmune thyroiditis: Effects of in vitro modulation by rosiglitazone and dexamethasone
Mary Ann Liebert Inc.
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Background: In Hashimoto's thyroiditis (HT), there is evidence for activation of peripheral T-lymphocytes that predominantly express a T helper 1 (TH1) cytokine bias. However, the immunomodulatory factors involved in regulating this response have so far received scant attention. In this study, we examine the effects of the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand, rosiglitazone on the expression of interferon (IFN)-γ (TH1) and interleukin (IL)-4 (TH2) by activated peripheral CD4+ and CD8+ lymphocytes in patients with HT (n = 10) and healthy control subjects (n = 12). Methods: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or absence of varying doses of dexamethasone and rosiglitazone (0.01 µM, 1.0 µM, and 100 µM). Cytokine expression was determined by flow cytometry. Results: CD4+ and CD8+ IFN-γ expression was greater in HT than controls (14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A dosedependent inhibition of IFN-γ expression was seen with dexamethasone and rosiglitazone. Inhibition of CD4+ and CD8+ IFN-γ expression with both dexamethasone and rosiglitazone was greater in control subjects than in patients (p < 0.05). There was no significant difference in IL-4 expression between patients and control groups and its expression remained unaffected by either compound. Conclusions: We show that CD4+ and CD8+ T lymphocytes from HT patients express a type 1 cytokine bias that is significantly more resistant to in vitro modulation by rosiglitazone and dexamethasone. Further studies are needed to clarify if this resistance plays a role in the pathogenesis of autoimmune thyroid disease (AITD).
Okosieme, O.E., Parkes, A.B., Premawardhana, L.D.K.E., Thomas, A.W., Evans, L.M. and Lazarus, J.H. (2006) 'Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro modulation by rosiglitazone and dexamethasone', Thyroid, 16(10), pp.953-960
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