-
[show abstract]
[hide abstract]
ABSTRACT: To assess the usefulness of circulating IL-16 and RANTES measurements as markers of Graves' orbitopathy (GO) activity and to estimate the role of these cytokines in GO pathogenesis.
42 individuals were divided into four groups: Group 1 comprised 15 euthyroid patients with clinical symptoms of GO who underwent corticosteroid therapy consisting of intravenous infusions of methylprednisolone (MP) and teleradiotherapy (TR); Group 2 comprised ten patients with hyperthyroid GD (Gtx); Group 3 comprised ten patients with GD in euthyreosis (Geu); and Group 4 comprised seven healthy volunteers age- and sex-matched to Groups 1-3. Serum samples were collected 24 hours before the first dose of MP, 24 hours after the first dose of MP, before TR, and at the end of therapy. Serum IL-16 and RANTES were determined by ELISA and TSH-Rab by RIA.
Serum IL-16 levels in patients with GO were significantly elevated at the end of therapy: 346 pg/mL (257-538) compared to IL-16 values before treatment: 250 ng/mL (211-337) and to the control group. RANTES serum concentrations did not significantly differ between studied groups, and immunosuppressive treatment did not influence its level. A negative correlation between TSH-Rab and RANTES was found in all studied groups (R = -0.32, p 〈 0.01).
Our data suggests that IL-16 may exert an immunoregulatory effect in Graves' orbitopathy. Serum measurements of both IL-16 and RANTES may be clinically useful; however, establishing their place in the diagnostics and treatment monitoring of GO needs further research.
Endokrynologia Polska 01/2012; 63(2):92-6. · 1.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Thyrotoxicosis is more frequent in postmenopausal women than in the general population, effectively accelerating bone turnover. Interleukin-6 has been shown to be involved in the pathogenesis of bone disorders. Thus, the aim of the present study was to assess the role of IL-6 and its soluble receptor in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women.
The study was carried out in 40 subjects with toxic nodular goitre in three groups: Group 1 - 13 premenopausal females, mean age 36 ± 15 years (PremTx→PremEu); Group 2 - 12 postmenopausal females, mean age 66 ± 14 years (PostTx→PostEu); and Group 3 - 15 males, mean age 45 ± 21 years (MTx→MEu). Overt thyrotoxicosis and euthyreosis after treatment with thyrostatics were confirmed by thyrotropin, free thyroxine and free triiodothyronin concentrations. Serum levels of bone turnover markers: TRACP5b and osteocalcin as well as serum IL-6 and IL-6sR were determined using ELISA kits.
TRACP5b/osteocalcin quotient was significantly elevated in the PostTx females compared to the PremTx women (p < 0.02). There was a positive correlation between serum TRACP5b and osteocalcin in the studied patients (R = 0.45, p < 0.001). Levels of serum IL-6 values were significantly elevated in PostTx: 3.0 (2.14-6.40) and MTx: 2.24 (1.60-5.10), compared to PremTx females: 1.39 (0.96-2.14) (p < 0.01 and p < 0.05 respectively). There were significant positive correlations between IL-6 and IL-6sR concentrations (R = 0.22, p < 0.05) and between IL-6sR and TRACP5b serum levels (R = 0.23, p < 0.05).
The results of our study suggest that interleukin-6 plays a considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women.
Endokrynologia Polska 01/2011; 62(4):299-302. · 1.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO). The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice.
Folia Histochemica et Cytobiologica 12/2010; 48(4):549-54. · 0.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of the study was to evaluate the percentage of CD4+/CD8+ peripheral T cells expressing CD62L+ and CD54+ in patients with Graves' disease and to assess if these estimations could be helpful as markers of active ophthalmopathy. The study was carried out in 25 patients with Graves' disease (GD) divided into 3 groups: 1/ 8 patients with active Graves' ophthalmopathy (GO) (CAS 3-6, GO complaints pound 1 year), 2/ 9 patients with hyperthyroid GD without symptoms of ophthalmopathy (GDtox) and 3/ 8 patients with euthyroid GD with no GO symptoms (GDeu). The control group consisted of 15 healthy volunteers age and sex matched to groups 1-3. The expression of lymphocyte adhesion molecules was evaluated by using three-color flow cytometry. In GO group the percentage of CD8+CD54+, CD8+CD62L+, CD4+CD54+ and CD4+CD62L+ T cells was significantly higher as compared to controls (p<0.001, p<0.05, p<0.01, p<0.001 respectively). The percentage of CD8+CD54+ T lymphocytes was also elevated in GO group in comparison to hyperthyroid GD patients (p< 0.05). CD4+CD62L+ and CD8+CD54+ percentages were also increased in GDtox and GDeu as compared to controls. We found a positive correlation between the TSHRab concentration and the percentage of CD8+CD62L+ T cells in all studied groups (r= 0.39, p<0.05) and between the TSHRab level and CAS (r= 0.77, p<0.05). The increased percentage of CD8+CD54+ and CD8+CD62L+ T cells in patients with Graves' ophthalmopathy may be used as a marker of immune inflammation activity.
Folia Histochemica et Cytobiologica 01/2009; 47(1):29-33. · 0.81 Impact Factor
-
Janusz Mysliwiec,
Robert Zbucki,
Maria Winnicka,
Boguslaw Sawicki,
Agnieszkar Nikolajuk,
Karol Kaminski,
Piotr Mysliwiec,
Wlodzimierz Musial,
Zofia Bondyra,
Jerzy Walecki,
Maria Gorska
[show abstract]
[hide abstract]
ABSTRACT: Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by an imbalance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) and osteocalcin in IL-6-deficient mice to assess the role of IL-6 in bone metabolism in hypothyroidism in mice. C57BL/6J (wild-type; WT) and C57BL/6J(IL6-/-Kopf) (IL-6 knock-out; IL6KO) mice randomly divided into 4 groups with 10 in each one: 1/ WT mice in hypothyroidism (WT-ht), 2/ WT controls, 3/ IL6KO mice with hypothyroidism (IL6KO-ht) and 4/ IL6KO controls. Experimental model of hypothyroidism was induced by intraperitoneal injection of propylthiouracyl. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentrations of TRACP 5b (median and interquartile ranges) were significantly decreased in both groups of mice with hypothyroidism: WT (3.2 (2.5-4.7) U/l) and IL6KO (2.6 (1.8-3.5) U/l) as compared to the respective controls. Similarly, serum osteocalcin levels were significantly reduced in both groups of mice in experimental hypothyroidism: WT (25.8 (23.0-28.2) ng/ml) and IL6KO (21.5(19.0-24.6) ng/ml) in comparison to the respective controls. There were no significant differences in bone turnover markers between IL6KO and WT mice both in hypothyroid and control animals. The results of the present study suggest that IL-6 does not play an important role in bone turnover in both euthyroid and hypothyroid mice.
Folia Histochemica et Cytobiologica 02/2007; 45(4):387-92. · 0.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Activated CD4 T cells' express CD40 ligand (CD154) interacting with CD40 on the B cells surface, protecting them from Fas-mediated apoptosis and in this study, influence humoral response. The aim of the study was to assess soluble CD40 and CD154 in Graves' disease (GD) and Hashimoto's thyroiditis (HT) in relation to Fas and FasL and to the markers of humoral response: aTPO, aTG and aTSHR. The study was carried out in 5 groups of subjects: 1/14 patients with GD in euthyreosis on methimazol (euGD), 2/20 patients with hyperthyroid GD (hrGD), 3/15 patients with HT in euthyreosis on levothyroxine (euHT), 4/16 patients with hypothyroid Ht (hoHT), 5/12 healthy volunteers, age and sex-matched to groups 1-4. The serum levels of CD40, CD154, Fas and FasL, aTPO and aTG were determined by ELISA and aTSHR was determined by the RIA method. CD40 serum concentration was significantly higher in hoHT individuals: 55.8 (24.0-83.2) pg/ml (p<0.01) and euHT patients: 51.2 (20.0-80.1) (p<0.05) as compared to the controls. Also sCD40L values were significantly increased in euHT individuals: 5.1 (1.0-11.8) (p<0.05) and hoHT patients: 3.9 (0.7-11.2) ng/ml (p<0.05) as compared to the controls. There was a positive correlation between sCD40 and sCD154 in the patients studied (r=0.36, p<0.001). In HT patients we found positive correlations between sCD40 and aTPO (r=0.45, p<0.001) and sFas (r=0.36, p<0.05) as well as a negative correlation between sCD40 and FasL (r=-0.24, p<0.05). In GD patients there was a positive correlation between sCD40 and aTSHR (r=0.28, p<0.05). In summary, our results suggest that CD40/CD154 interaction plays an important role in the regulation of autoimmune humoral response, both in Hashimoto's thyroiditis and Graves' disease. Fas-mediated apoptosis seems to be involved in this process especially in Hashimoto thyroiditis. Soluble CD40 may serve as a marker of the active stage of autoimmune thyroid disease.
Immunological investigations 01/2007; 36(3):247-57. · 1.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It was recently suggested that genetic factors could play a major role in the development of Graves' disease (GD). The aim of the present study was to evaluate the frequency of the c.721G-->A polymorphism and the c.1405A-->G polymorphism of the intercellular adhesion molecule 1 (ICAM-1) gene in subjects with GD compared with that in healthy controls, because ICAM-1 was found to play a key role in lymphocyte infiltration into the thyroid gland and the concentration of the soluble form of ICAM-1 correlates significantly with the clinical activity and treatment status in GD. We have analyzed the association of ICAM-1 polymorphisms with the age at onset of GD and the presence of ophthalmopathy. In a group of 235 patients with GD and 211 healthy controls we have shown that polymorphism at position c.721G-->A is associated with an earlier age of GD onset and that the c.1405A-->G polymorphism of the ICAM-1 gene could predispose to Graves' ophthalmopathy. This suggests that G241R and K469E amino acid substitutions in the ICAM-1 molecule could influence the intensity/duration of the autoimmunity process and the infiltration of orbital tissues. It could be speculated that therapy that modulates ICAM-1 function may delay the onset and/or prolong the remission and/or have an influence on clinical manifestations of GD.
Journal of Clinical Endocrinology & Metabolism 10/2003; 88(10):4945-9. · 6.50 Impact Factor
