title: Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro modulation by rosiglitazone and dexamethasone.
abstract: BACKGROUND
  In Hashimoto's thyroiditis (HT), there is evidence for activation of peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) 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-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon (IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) 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 microM, 1.0 microM, and 100 microM). Cytokine expression was determined by flow cytometry.
  
  
  RESULTS
  CD4(+) and CD8(+) IFN-gamma 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 dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma 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).
authors.affiliation: Centre for Endocrine and Diabetes Science, School of Medicine, Cardiff University, Cardiff, United Kingdom. okosiemeoe@cf.ac.uk
authors.forename: O E
authors.initials: OE
authors.lastname: Okosieme
authors.forename: A B
authors.initials: AB
authors.lastname: Parkes
authors.forename: L D K E
authors.initials: LD
authors.lastname: Premawardhana
authors.forename: A W
authors.initials: AW
authors.lastname: Thomas
authors.forename: L M
authors.initials: LM
authors.lastname: Evans
authors.forename: J H
authors.initials: JH
authors.lastname: Lazarus
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000627:therapeutic use; D050031:Hashimoto Disease / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013967:Thyroiditis, Autoimmune / Q000188:drug therapy* / Q000235:genetics
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate