Serum Th1 and Th2 profile cytokine level changes in patients with Graves' ophthalmopathy treated with corticosteroids.
ABSTRACT The aim of this study was to estimate the influence of corticosteroids on Th1 and Th2 serum cytokine balance in patients with GO: IFNgamma, TNFalpha, IL-4 and IL-10. Further, we tested the hypothesis of an up-regulation of Th2 immune response during successful treatment with corticosteroids to explain their beneficial effect in Graves' ophthalmopathy. Serum cytokines were detected in three groups of subjects: 20 patients with Graves' disease without ophthalmopathy (Gd), 16 patients with clinical symptoms of ophthalmopathy (GO) (CAS over 3 points, last consultation record for GO less than a year old) and 16 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) (2 series, 3 g each time) and subsequent treatment with oral prednisone (60 mg per day) in a tapering schedule. The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and at the end of corticosteroid therapy. The levels of IFNgamma, TNFalpha, IL-4 and IL-10 in the serum were determined using ELISA. Statistical significance was estimated by the Mann-Whitney U-test. Our findings show a deviation to systemic Th2 profile cytokines in Graves' disease. In patients with GO, we found a significantly increased serum IL-10 concentration. In corticosteroid-responsive patients, the balance of serum cytokines IL-4/IFNgamma, IL-4/TNFalpha, IL-10/IFNgamma and IL-10/TNFalpha increased and remained upregulated until the end of the study. In non-responders, the balance of serum cytokines studied increased after methylprednisolone but declined markedly during continuation of the therapy with prednisone. In summary, our results show that efficient corticosteroid therapy may be related to its influence on Th2/Th1 profile cytokine balance. The upregulation of serum IL-4 and IL-10 during successful treatment with corticosteroids indicate the possibility of using these cytokines as predictors of the beneficial effect of corticosteroids in Graves' ophthalmopathy.
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ABSTRACT: Interleukin-18 (IL-18), a novel cytokine of the IL-1 family, and TGFbeta1 have been lately identified in several thyroid autoimmune diseases. The aim of this study was to estimate the influence of corticosteroids on serum IL-18 and TGFbeta1 in Graves' ophthalmopathy (GO) patients and to assess their potential as a guideline of immunosuppressive therapy. The study was carried out in three groups of subjects: (1). 17 patients with clinical symptoms of ophthalmopathy (GO) that underwent corticosteroid therapy consisting of intravenous methylprednisolone (MP) infusions and subsequent treatment with oral prednisone (P); (2). 14 patients with euthyroid Graves' disease (Gd) without symptoms of ophthalmopathy; (3). 12 healthy volunteers age- and sex-matched to groups 1 and 2. The serum levels of IL-18 and TGF beta1 were determined by the ELISA method. Thyroid receptor antibodies (TRAB) were estimated by the RIA method. Levels of IL-18 were significantly higher in both GO [340+/-109 pg/ml (p<0.02)] and Gd individuals [308+/-89 pg/ml (p<0.05)] as compared to the control group (238+/-88 pg/ml). There were no significant differences in TGFbeta1 concentrations between studied groups. TRAB values were significantly increased in both GO (p<0.001) and Gd individuals (p<0.001) as compared to the controls. In coticosteroid-responsive patients we have found a significant decrease in IL-18 serum concentration as compared to the pretreatment values. We did not find any correlation between IL-18 or TGFbeta1 and TRAB, duration of GO, clinical activity score (CAS) or proptosis. Our results suggest that efficient corticosteroid therapy in patients with Graves' ophthalmopathy may be related to its influence on systemic IL-18.International Immunopharmacology 04/2003; 3(4):549-52. · 2.42 Impact Factor
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ABSTRACT: Interactions between cytokines play an important role in the development of thyroid autoimmunity. Using enzyme-linked immunosorbent assay we investigated serum concentrations of soluble interleukin-2 receptor (sIL-2R), interferon-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10, CD30, monokine induced by interferon-gamma (MIG), cytotoxic T lymphocyte antigen-4 and markers of apoptosis decoy receptor 3 and Bcl-2 in 28 patients with hyperthyroid Graves' disease (GD), 24 patients with untreated Hashimoto's thyroiditis (HT) and 15 healthy controls. TNF-alpha, IL-10 and sIL-2R were higher in GD compared with HT and controls (TNF-alpha: 8.79 in GD versus 2.54 pg/ml in HT, P = 0.01; IL-10: 10.00 versus 3.10 versus 3.10 pg/ml, P(1) < 0.001, P(2) = 0.005; sIL-2R: 1.26 versus 0.64 versus 0.46 ng/ml, P < 0.001). MIG and CD30 were higher in HT compared with controls (649.22 +/- 262.55 versus 312.95 +/- 143.35 pg/ml, P = 0.037, 6.57 +/- 2.35 versus 3.03 +/- 1.04 U/ml, P = 0.036 respectively). In GD sIL-2R decreased when the euthyroid state was achieved (1.31 +/- 0.64 versus 0.260 +/- 0.11, n = 12, P < 0.001). sIL-2R correlated positively with free thyroxine (FT4) (R = 0.521, P = 0.000) and negatively with thyroid stimulating hormone (TSH) (R = -0.472, P = 0.00132). MIG correlated negatively with FT4 (R = -0.573, P = 0.00234) and positively with TSH (R = 0.462, P = 0.0179). The results suggest that serum concentrations of sIL-2R and MIG are related to thyroid function rather than to activation of autoimmunity.Clinical & Experimental Immunology 02/2009; 156(2):211-6. · 3.41 Impact Factor
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ABSTRACT: Perioperative renal dysfunction following abdominal aortic aneurysm (AAA) repair is multifactorial and may involve hypotension, hypoxia and ischaemia-reperfusion injury. Studies of cardiac and hepatic transplant surgery have demonstrated beneficial effects on renal function of high-dose methylprednisolone administered before surgery. Twenty patients undergoing elective open AAA repair were randomized to receive either methylprednisolone 10 mg/kg or dextrose (control) before induction of anaesthesia. Blood was analysed for a panel of cytokines representative of T helper cell type 1 and 2 subsets. Urine was analysed for subclinical markers of renal dysfunction (albumin, alpha(1)-microglobulin and N-acetyl-beta-D-glucosaminidase). Data from 18 patients were analysed. Both groups demonstrated glomerular and proximal convoluted tubular dysfunction that was unaffected by steroid treatment. Steroid administration increased serum levels of urea and creatinine (both P < 0.001). The steroid group had increased interleukin 10 levels (P = 0.005 compared to controls). There were no differences between groups in overall surgical complications, length of intensive care unit (P = 0.821) and hospital (P = 0.719) stay, or 30-day mortality. Methylprednisolone administration altered the cytokine profile favourably but adversely affected postoperative renal function.British Journal of Surgery 01/2008; 95(1):50-6. · 4.84 Impact Factor