Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amiodarone-induced thyrotoxicosis (AIT) occurs both in abnormal thyroid glands (nodular goiter, latent Graves' disease) (type I AIT) or in apparently normal thyroid glands (type II AIT). Differentiation of the two forms is crucial, because type I AIT responds well to methimazole and potassium perchlorate combined treatment, whereas type II AIT is effectively managed by glucocorticoids. Differential diagnosis is often difficult, although thyroid radioactive iodine uptake is usually low-to-normal in type I and low-suppressed in type II, and serum interleukin-6 levels are normal/slightly elevated in type I, markedly elevated in type II. Color flow Doppler sonography (CFDS) is a technique that shows intrathyroidal blood flow and provides real-time information on thyroid morphology and hyperfunction. To investigate the usefulness of CFDS in differentiating the two types of AIT, 27 consecutive AIT patients, 11 type I and 16 type II, were evaluated by CFDS before starting antithyroid treatment. Gender, age, severity of thyrotoxicosis, and cumulative amiodarone dose were similar in the two groups. All type II AIT patients had a CFDS pattern 0 (ie, absent vascularity), in agreement with the pathogenesis of the disease, due to thyroid damage. Likewise, nine patients with subacute thyroiditis, another destructive process of the thyroid gland, also had a CFDS pattern 0. Eleven patients with type I AIT had a CFDS pattern ranging from pattern I (presence of parenchymal blood flow with patchy uneven distribution) (7 patients, 64%) to pattern II (ie, mild increase of color flow Doppler signal with patchy distribution) (1 patient, 9%) and pattern III (markedly increased color flow Doppler signal with diffuse homogeneous distribution)(3 patients, 27%), similar to that found in patients with untreated Graves' disease patients, thus indicating a hyper-functioning gland. Control subjects and euthyroid patients under long-term amiodarone treatment had absent thyroid hypervascularity and a CFDS pattern 0. These findings demonstrate that CFDS distinguishes type I and II AIT. Because of its rapidity and noninvasive features, CFDS represents a valuable tool for a quick differentiation between the two types of AIT. This can avoid any delay in initiating the appropriate treatment for a rapid control of thyrotoxicosis in patients whose tachyarrhythmias or other cardiac disorders make thyroid hormone excess extremely deleterious.
 ...
PMID:Color flow Doppler sonography rapidly differentiates type I and type II amiodarone-induced thyrotoxicosis. 929 40

Interleukin-6 (IL-6) is a cytokine released by thyrocytes and is involved in disease processes such as autoimmune thyroid disease. The secretion of IL-6 can be stimulated by interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF), serum, TSH and agents which increase intracellular cyclic AMP levels. Antithyroid drugs such as methimazole inhibit IL-6 production by thyrocytes but the effects of glucocorticoids and oestrogen have not been investigated. The effects of dexamethasone and 17 beta-oestradiol on IL-1-, TNF-, TSH-, forskolin- and phorbol 12-myristate 13-acetate (PMA)-stimulated IL-6 release in serum-free conditions were studied in human thyrocytes derived from patients with Graves' disease and toxic multinodular goitres, and in the immortalised human thyrocyte cell line, HTori3. Dexamethasone inhibited IL-6 production under stimulated conditions. In serum-free conditions, no basal release of IL-6 was assayable. In all but one of the primary thyroid cultures, TSH did not stimulate IL-6 release above the lower detectable limit of the assay. In Graves' and multinodular goitre thyrocytes, inhibition of IL-1 (100 U/ml)-stimulated IL-6 release by dexamethasone (100 nmol/l) was 62.51% +/- 10.43 (S.E.M.), and in HTori3 cells it was 78.35% +/- 3.9. The degree of IL-1 stimulation of IL-6 release and inhibition by dexamethasone was not significantly different in thyrocytes derived from either Graves' or multinodular glands. 17 beta-Oestradiol had no effect on IL-1-stimulated IL-6 release in either primary thyroid cell culture or in HTori3 cells.
 ...
PMID:Effect of glucocorticoids and oestrogen on interleukin-6 production by human thyrocytes from patients with Graves' disease and toxic multinodular goitre and from HTori3 cells. 936 13

We report 11 cases of amiodarone-induced hyperthyroidism. We tried to classify them into 2 groups, according to Bartelena et al. (JCEM 81: 2930, 1996). The serum level of interleukin-6 (IL-6) was measured in 7 patients by an immunoenzymometric assay. In type I (cases 1-3) the thyroid was abnormal (goiter, Graves' disease) but IL-6 levels were normal. These cases were successfully managed by the combined use of thionamide drugs (carbimazol or propylthioruacil = PTU) and potassium perchlorate. In type II (case 4), the thyroid seemed to be normal but the serum level of IL-6 was increased, possibly due to a destructive thyroiditis. Treatment with prednisone (40 mg/day) and PTU resulted in a prompt normalization of T3. Contrary to Bartalena et al., we observed cases with normal thyroid and normal levels of IL-6 (cases 5-8) (type III). In these cases prednisone (40 mg/day for 2 weeks) was ineffective but the combined use of thionamide drugs and perchlorate was associated with a normalization of thyroid hormones. This combined treatment seems to be effective in most patients (type I, III). In case of failure of this treatment, a high dose of prednisone (1 mg/kg) could be tried or a lower dosage (40 mg/day) could be used in cases with high IL-6 levels (type II).
 ...
PMID:[Treatment of amiodarone-induced hyperthyroidism: corticosteroids or potassium perchlorate? What value do interleukin-6 levels have?]. 944 65

In order to examine which cytokine could be used as a marker of the biological effect of thyroid hormones or anti-thyroid antibodies in Graves' disease (GD) patients, we simultaneously evaluated the concentrations of TSH, free thyroid hormones (fT3 and fT4), anti-thyroid antibodies (anti-TPO and anti-TG) and a group of cytokines: interleukin-2 (IL-2), tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and their soluble receptors (sIL-2R, sTNFalphaR, sIL-6R) as well as interleukin-10 (IL-10) in eight GD females and nine normal controls. We found that serum sIL-2R concentrations of GD patients had only the tendency to be higher versus controls, but strong positive correlations between fT3 and fT4 and sIL-2R in peripheral blood of GD subjects were revealed. We showed that sIL-2R was the best cytokine marker, showing very good correlation with the endocrine status of GD patients.
 ...
PMID:Cytokines serum levels as the markers of thyroid activation in Graves' disease. 955 56

Postpartum thyroid dysfunction (PPTD) is an autoimmune-mediated thyroid destructive process. Human interleukin-6 (IL-6) is a cytokine found to be increased in subacute thyroiditis, amiodarone-induced thyrotoxicosis, Graves' disease, and other thyroid destructive processes. We report serum IL-6 levels in PPTD in two independent studies. New York Study: In a previous prospective study we demonstrated that PPTD occurred in 25% (7/28) of women with type 1 diabetes mellitus. IL-6 determinations were made on the frozen serum samples of these 28 women during each trimester of their pregnancy and at 1.5, 3, 6, 9, and 12 months postpartum. IL-6 levels were found to be similar in women with PPTD compared with women without PPTD (mean 3.06+/-2.25 vs. 2.51+/-2.21 pg/mL; p = 0.15). No difference in IL-6 levels was found between the pre- and the postpartum periods (mean 2.67+/-1.82 vs. 3.04+/-2.44 pg/mL; p = 0.30) in all 28 women. Cardiff Study: Serum IL-6 levels were measured on frozen serum samples of 30 women with PPTD. IL-6 levels were below the detection limit (25 fmol/L or 0.65 pg/mL) in 94 (67%) of these samples. No significant difference in the mean serum IL-6 levels were found between any time points in the study. There was no correlation between serum IL-6 levels, thyroid peroxidase (TPO)- antibodies and serum thyrotropin (TSH) levels at any time point. IL-6 levels during pregnancy or postpartum were not found to be significantly different in women with PPTD compared with women without PPTD.
 ...
PMID:Interleukin-6 levels are not increased in women with postpartum thyroid dysfunction. 962 26

Cytokines might be involved in the immunological flare up, seen in some patients after 131I-treatment. Therefore, we measured serum levels of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interleukin-6 soluble receptor (IL-6sR) and Intercellular-adhesion-molecule-1 (ICAM-1) as well as tumor necrosis factor (TNF-alpha) after 131I-treatment of Graves' disease and nodular goiter. Seven patients with Graves' disease, eight with toxic nodular goiter and seven with non-toxic nodular goiter, were followed after 131I-treatment. The patients were treated in the euthyroid state. Blood samples were drawn at day 0, 4, 7, 21 and after 3 months. Significant increases were seen in free T4 index (FT4I), free T3 index (FT3I) and thyroglobulin (Tg) within the first weeks, and TSH simultaneously decreased. None of the cytokines demonstrated any change during follow-up, neither in the entire group nor in subgroups. FT4I and FT3I correlated significantly to ICAM-1. In conclusion, our data suggest that there does not seem to be prolonged cytokine activation after 131I-treatment for thyroid disorders.
 ...
PMID:Serum levels of the cytokines IL-1beta, IL-6 and ICAM-1 after 131I-treatment of Graves' disease and nodular goiter. 1096 35

The mechanism of action of the immunosuppressive effects of antithyroid drugs has remained a matter of controversy, despite our earlier contention that such effects in vivo were indirect; ie., it was our view that the drugs were acting on the thyroid cells, reducing their thyroid hormone production and other activities, with a consequent reduction in thyrocyte-immunocyte signalling. The reduction in the activation of CD4+ cells,the increased number and activation of CD8+ (and CD8+CDllb+) cells, and the reduction of soluble interleukin-2 receptors, thought once to be direct effects of the medication, are now shown to be due to amelioration of the hyperthyroidism. Thus the reduction in thyroid hormone production induced by the drugs is central to these actions. In addition, the iodination of thyroglobulin is inhibited by these agents, which may affect antigen presentation by the thyrocyte. Furthermore, there is now evidence that the thionamides interfere with thyrocyte expression of such molecules as Class I antigen, interleukin-1, interleukin-6, prostaglandin E2, and heat shock protein. The expression of thyrocyte Class II antigen is probably not inhibited by these drugs, although one group has shown that lectin-stimulated thyrocyte Class II expression is diminished by this treatment; this group postulated that this effect might be mediated by reduced interferon gamma production by T lymphocytes, but in vitro experiments do not corroborate this proposal. In any event, the actions as described of the effects of antithyroid drugs on the thyroid cells (particularly normalization of thyroid function) would certainly suffice to explain the diminution of thyroid antibodies (including thyroid stimulating antibody), the reduced immunological response, and the increased remission rate in Graves disease as a consequence of antithyroid drug therapy, without the need to invoke a direct immunosuppressive effect.
 ...
PMID:The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte-immunocyte signalling: a review. 1128 52

To investigate whether amiodarone increases interleukin-6 (IL-6) production in thyrocytes, human follicles obtained from subtotally thyroidectomized patients with Graves' disease were cultured in serum-free medium supplemented with various concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles gradually formed monolayer cells and secreted triiodothyronine (T3), thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-dependently increased T3 and Tg but not IL-6 levels in the conditioned medium. Amiodarone exerted no significant effect on T3, Tg, or IL-6 concentrations at 0.1-1 microM. In contrast, at 10-20 microM, it decreased T3 and Tg, but increased IL-6 levels, and these changes were accompanied by increased expression of IL-6 mRNA. Amiodarone-induced IL-6 production was inhibited by prednisolone at 10(-7) M. Electron microscopic examination revealed that the thyroid follicles in the suspension culture remained intact at 1 microM, but that cytotoxic effects (decreased microvilli and increased onion-like inclusion bodies) occurred at higher concentrations (10-25 microM). These in vitro findings indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 microM), but exerts cytotoxic effect by inducing the production of a proinflammatory cytokine (IL-6) at higher concentrations. Because amiodarone-induced IL-6 production was inhibited by prednisolone, it is reasonable to administer glucocorticoids to patients with amiodarone-induced destructive thyrotoxicosis (type II).
 ...
PMID:Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture. 1128 78

It has been shown that human thyrocytes can synthesize cytokines which activate T and B lymphocytes. These immune cells play important roles in the initiation and continuation of thyroid autoimmunity. The aim of this study was to estimate serum concentrations of soluble interleukin-6 receptor (sIL-6R), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients with Graves' disease (GD) (n=44, mean age 14.8 years), in patients with nontoxic nodular goiter (NTNG) (n=36, mean age 15.6 years) and in a group of healthy controls (n=20, mean age 14.5 years). ELISA was used to determine the concentration of cytokines, antithyroglobulin and antithyroid peroxidase antibodies in patients with thyroid disease. Radio receptor assay (RRA) was performed to detect anti-TSH receptor autoantibodies (TRAb). Serum levels of IL-6, sIL-6R and IL-8 were markedly elevated in patients with GD before treatment with methimazole (p<0.0001 for IL-6, p<0.006 for sIL-6R, p<0.004 for IL-8) and after 8 weeks of therapy (p<0.011 for IL-6, p<0.04 for IL-8). However, following 24 months of treatment, normal serum concentrations of these cytokines were restored. Furthermore, patients with NTNG showed a slightly elevated concentration of cytokines (IL-6, IL-8). Serum levels of tri-iodothyronine in patients with GD positively correlated with serum concentrations of IL-6 (r = 0.35, p<0.025) and sIL-6R (r = 0.31, p<0.047), while no correlation was found between thyroxine and cytokines. Moreover, we observed a positive correlation between serum levels of TPO-Abs, TRAb and IL-6 (r = 0.43, p<0.008; r = 0.5, p<0.003) and between TPO-Abs and IL-8 (r = 0.67, p<0.0001). However, in patients with NTNG no correlation was observed between serum levels of antithyroid antibodies or thyroid hormones and serum levels of cytokines. We conclude that the cytokines (IL-6, sIL-6R, IL-8) could play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.
 ...
PMID:Serum levels of cytokines in children and adolescents with Graves' disease and non-toxic nodular goiter. 1145 24

The TSH receptor (TSHR) is the autoantigen responsible for the hyperthyroidism of Graves' disease. However, whether this receptor plays a role in the development of Graves' ophthalmopathy (GO) is unclear. Expression of TSHr is augmented in orbital tissues from patients with GO, and in newly differentiated adipocytes derived from precursor cells within the orbit. Our recent studies suggest that interleukin-6 (IL-6), a cytokine elevated in the circulation of Graves' patients, stimulates TSHr expression in vitro in orbital preadipocyte fibroblasts. This cytokine might play a role in the pathogenesis of GO by stimulating TSHr expression within the fatty connective tissues of the orbit, allowing the receptor to act there as an autoantigen. Whether IL-6 also stimulates adipogenesis in the orbit is unclear at present, but such an effect could contribute to the increased volume of orbital adipose/connective tissue characteristic of this condition. Other cytokines, including IFN-gamma and TGF-beta, inhibit TSHr expression and adipogenesis by orbital fibroblasts, effects that would seem to favor disease remission. The initiation and subsequent clinical severity of GO may therefore be influenced by competing inhibitory and stimulatory cytokine effects occurring simultaneously within the orbit. Some of these may impact the expression of TSHr, the putative orbital autoantigen in this condition.
 ...
PMID:Thyrotropin receptor expression in orbital adipose/connective tissues from patients with thyroid-associated ophthalmopathy. 1195 38


<< Previous 1 2 3 4 Next >>