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

Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular cAMP accumulation and protein synthesis. These data have been found true in any thyroid system studied so far, both in terms of immunologic and enzymatic activity of TPO. TSH and cAMP also increase the levels of the specific mRNA for TPO in thyroid cells from different species. Whether this phenomenon is due to a direct transcriptional regulation of the TPO gene, as shown in dog thyroid cells, or to posttranscriptional effects, as it would appear in FRTL-5 cells, remains to be clarified by future experiments. Thyroid stimulating antibody (TSAb) of Graves' disease also stimulates the expression of M/TPO-Ag. This finding gives further support to the relevance of TSAb in the pathogenesis of hyperthyroidism and explains the well known observation that the "microsomal" antigen is particularly abundant in glands of Graves' patients. The modulation of M/TPO-Ag surface expression by TSH can explain the decrease of circulating anti-MAb observed during L-thyroxine therapy in hypothyroid patients with Hashimoto's thyroiditis. Other agents, such as methimazole and sodium iodide, which influence thyroid cell function, do not directly interfere with the expression of M/TPO-Ag. Cytokines, such as gamma-interferon, interleukin-1, and interleukin-6 have been shown to inhibit the TSH-induced increase of TPO mRNA, but further investigations are required to elucidate the exact role of cytokines in the regulation of M/TPO-Ag expression.
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PMID:The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. 166 95

Autoimmune thyroiditis is characterized by lymphocytic accumulation within the thyroid which may be the result, in part, of immunomodulatory cytokine secretion by thyrocytes. We have tested human thyroid cell cultures (n = 9) for interleukin-6 (IL-6) release using two bioassays. IL-6 was detected in all culture supernatants under basal conditions and was increased by gamma-interferon, tumour necrosis factor and TSH in a dose-dependent manner. The bioactivity was confirmed as IL-6 by immunoblotting experiments and could not be accounted for by contamination of the thyroid cell cultures with fibroblasts, lymphocytes or monocytes. Circulating IL-6 levels were not raised in patients with Graves' hyperthyroidism. Exogenous recombinant IL-6 reduced cyclic AMP production in response to TSH when added to thyroid cell cultures. Since IL-6 plays a major role in B cell differentiation and T cell activation, release of IL-6 by thyrocytes may increase the intrathyroidal autoimmune response in Graves' disease and Hashimoto's thyroditis. Our results also suggest that IL-6 may modulate thyroid cell function.
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PMID:Regulation of interleukin-6 release by human thyrocytes. 217 56

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, i.e., it was our view that the drugs were acting on the thyroid cells, reducing their hormone production and other activities, with a consequent reduction in thyrocyte-immunocyte signaling. The reduction in the activation of CD4+ cells, the increased number and activation of CD8+ (and CD8+CDIIb+) 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 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 antithyroid drugs on the thyroid cells, 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, without the need to invoke a direct immunosuppressive effect.
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PMID:Evidence that the immunosuppressive effects of antithyroid drugs are mediated through actions on the thyroid cell, modulating thyrocyte-immunocyte signaling: a review. 752 82

We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid tissues obtained from patients with autoimmune diseases or neoplastic thyroid disorders employing immunohistochemistry in sections from paraffin embedded tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells (TFEC) from papillary carcinomas (four of five patients) but not in follicular carcinomas (five patients). Interleukin-6 was also detected in non-toxic multinodular goiters (four of seven patients), in patients with Graves' disease who did not have an early recurrence of hyperthyroidism after surgery (three of four patients), in follicular adenomas (five of nine patients), in Hashimoto's thyroiditis (two out of six patients, both belonging to a group of three with an early stage of the disease), and in paraadenomatous tissues (in three of nine patients). Interleukin-1 alpha positive TFEC were found less frequently than interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few interleukin-6 and interleukin-1 alpha positive interstitial cells were found, even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or papillary carcinoma, whereas follicular cancer tissues were without interleukin-6 and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and interleukin-1 alpha were demonstrated in TFEC from patients with both Graves' disease and Hashimoto's thyroiditis, and the presence of these cytokines was related to the stage of the autoimmune process.
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PMID:Immunocytochemical localisation of interleukin-1 alpha and interleukin-6 in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders. 757 71

Amiodarone, an iodine-rich cardiac drug, may induce thyrotoxicosis (AIT), which can occur in patients with preexisting thyroid abnormalities and in subjects with apparently normal thyroid glands. The pathogenesis of AIT is often due to iodine-induced excessive thyroid hormone synthesis, especially in patients with underlying thyroid disease. In some instances, however, AIT may be related to a destructive process due to amiodarone-induced thyroiditis, resulting in thyroid cell damage and thyroid hormone release into the circulation. Another thyroid inflammatory process, subacute thyroiditis, has been recently reported to be associated with markedly increased serum interleukin-6 (IL-6) levels. To investigate the significance of serum IL-6 levels in AIT, we evaluated in a cross-sectional study the following subjects: 27 AIT patients, 15 with no apparent thyroid abnormalities (AIT-) and 12 with nodular goiter and/or thyroid autoimmune disease (AIT+); 14 euthyroid patients receiving chronic amiodarone therapy; 10 patients with amiodarone-induced hypothyroidism; 56 patients with spontaneous hyperthyroidism due to Graves' disease (n = 35) or toxic adenoma/nodular goiter (n = 21); 20 subjects with nontoxic goiter; and 50 healthy controls. Serum free thyroid hormone concentrations did not differ in patients with amiodarone-induced or spontaneous hyperthyroidism. Mean (+/- SE) serum IL-6 values were as follows: AIT-, 573.5 +/- 78.7 fmol/L (range, 149.4-1145.1); AIT+, 152.7 +/- 46.3 fmol/L (range, < 25-505.6); euthyroid patients receiving chronic amiodarone therapy, 51.4 +/- 10.0 fmol/L (range, < 25-122.5); amiodarone-induced hypothyroidism, 43.8 +/- 8.4 fmol/L (range, < 25-84.3); Graves' disease, 108.2 +/- 18.2 fmol/L (range, < 25-250); toxic adenoma/nodular goiter, 97.6 +/- 10.3 fmol/L (range, < 25-168.9); nontoxic goiter, 47.3 +/- 7.1 fmol/L (range, < 25-106.6); and controls, 37.8 +/- 6.2 fmol/L (range, < 25-99.4). Serum IL-6 values in AIT- patients were markedly higher (P < 0.0001) than those in all other groups. Values in AIT+, although slightly higher, did not significantly differ from those in patients with spontaneous hyperthyroidism. AIT- patients had low 24-h thyroidal radioiodine uptake (RAIU), whereas AIT+ had inappropriately low normal to high (9-58%) RAIU values in the presence of excess iodine. The presence of markedly elevated serum IL-6 concentrations and low thyroidal RAIU values in patients with AIT without underlying thyroid disease suggests the presence of amiodarone-induced thyroiditis as the etiology of thyrotoxicosis. Treatment of 2 such patients with prednisone was associated with a dramatic reduction and prompt normalization of IL-6 and thyroid hormone values.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Serum interleukin-6 in amiodarone-induced thyrotoxicosis. 810 31

Amiodarone-induced thyrotoxicosis (AIT) occurs in both abnormal (type I) and apparently normal (type II) thyroid glands due to iodine-induced excessive thyroid hormone synthesis in patients with nodular goiter or latent Graves' disease (type I) or to a thyroid-destructive process caused by amiodarone or iodine (type II). Twenty-four consecutive AIT patients, 12 type I and 12 type II, were evaluated prospectively. Sex, age, severity of thyrotoxicosis, and cumulative amiodarone dose were similar. Type II patients had higher serum interleukin-6 (IL-6; median, 440 vs. 173 fmol/L; P < 0.001), but lower serum thyroglobulin levels. Several weeks of thionamide therapy in eight type II or prolonged glucocorticoid administration in two type I patients had previously failed to control hyperthyroidism. Type II patients were given prednisone (initial dose, 40 mg/day) for 3 months and achieved normal free T3 and IL-6 after an average of 8 and 6 days, respectively. Exacerbation of thyrotoxicosis with increased serum IL-6 values, observed in 4 patients while tapering steroid, was promptly corrected by increasing it. Type I patients, given methimazole (30 mg/day) and potassium perchlorate (1 g/day), achieved normal free T3 and IL-6 concentrations after an average of 4 weeks. Exacerbation of thyrotoxicosis with markedly increased IL-6 was controlled by prednisone in 3 of 4 cases. Distinction of different forms of AIT is essential for its successful management. Type II AIT should be treated with glucocorticoids; type I AIT should be treated with methimazole and potassium perchlorate. Exacerbation of thyrotoxicosis, which may occur in both forms and is probably related to destructive processes, should be controlled by the addition/increase in glucocorticoids.
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PMID:Treatment of amiodarone-induced thyrotoxicosis, a difficult challenge: results of a prospective study. 876 54

To determine the possible involvement of interleukin-6 (IL-6) in the bone loss of hyperthyroidism, relationships between thyroid status, biochemical and densitometric parameters of bone metabolism, and IL-6 were studied in female subjects. Patients with hyperthyroidism caused by either toxic nodular goiter or Graves' disease had significantly higher serum IL-6 concentrations than normal controls. Within the control group, serum IL-6 was higher in postmenopausal than in premenopausal women, but this influence of menopausal status was not seen in the hyperthyroid patients. The production of IL-6 by blood mononuclear cells was higher in cells from the hyperthyroid women. Bone turnover was increased in the hyperthyroid patients based on serum osteocalcin and urinary deoxypyridinoline excretion, and the hyperthyroid group also had reduced radius bone mineral content (BMC). A subgroup of hyperthyroid patients who had the lowest BMC (values more than 1 SD below normal age-matched controls) also had serum IL-6 concentrations significantly greater than those of hyperthyroid patients showing less reduction of BMC. The correlations observed in this study support the possibility that IL-6 plays a role in mediating the bone loss that results from excess thyroid hormone.
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PMID:Serum interleukin-6 and bone metabolism in patients with thyroid function disorders. 898 37

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).
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PMID:[Treatment of amiodarone-induced hyperthyroidism: corticosteroids or potassium perchlorate? What value do interleukin-6 levels have?]. 944 65

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.
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PMID:The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte-immunocyte signalling: a review. 1128 52

Hyperthyroidism is associated with a higher incidence of arterial thromboembolism; increasing age, atrial fibrillation, and mitral valve abnormalities are risk factors. However, the contribution of endogenous coagulation parameters is unclear. Because thyroid hormone influences receptor and transcription factors, it can be expected that it will influence proteins involved in coagulation processes synthetised in many cells. Fourteen hyperthyroid patients were studied untreated, after 1 week of treatment with propranolol, and after therapeutic treatment with thiamazol. Fourteen matched controls were used for comparison. On each occasion, endothelial marker proteins, coagulation/fibrinolysis factors, and inflammatory (liver) markers were measured. Excess thyroid hormone was associated with elevated levels of most endothelium-associated proteins. In addition, plasma fibronectin and fibrinogen were increased, while plasminogen was decreased. No evidence was found that hyperthyroidism was associated with coagulation/fibrinolysis activation, or with increased levels of the inflammation markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) or C-reactive protein (CRP). Propranolol treatment only lowered the von Willebrand factor propeptide, and slightly increased plasminogen. Treatment with thiamazol returned all parameters to normal. Hyperthyroidism increased the plasma levels of most endothelial marker proteins, and of some liver-synthetized proteins. No evidence for coagulation/fibrinolysis activation was found. However, it appears that endothelial activation, which is indicative of a procoagulant state, is present in hyperthyroidism. This may explain the association between hyperthyroidism and thromboembolism especially if other risk factors are present. von Willebrand factor II (vWF:Ag-II) levels may be suitable markers to evaluate acute changes in endothelial function because this parameter responds more rapidly to changes in endothelial function than other factors.
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PMID:Endothelial function in patients with hyperthyroidism before and after treatment with propranolol and thiamazol. 1128 84


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