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)

Interleukin-1 is a potent inhibitor of thyroglobulin and cAMP production in human thyroid cells and the inhibitory effect is enhanced by tumor necrosis factor-alpha and interferon-gamma. In the present study secondary cultures of human thyroid cells produced interleukin-6 and the production was significantly increased after exposure of the cells to recombinant interleukin-1 alpha and -1 beta. This increase was dose-dependent and concomitant of the IL-1 induced decrease in cAMP and thyroglobulin production. Both tumor necrosis factor-alpha and -beta also augmented interleukin-6 production, but less potently than interleukin-1. Interferon-gamma did not affect the production of interleukin-6. The rat thyroid cell line FRTL-5 produced interleukin-6 spontaneously, and the production was enhanced after addition of recombinant interleukin-1 beta. A pathogenetic role of interleukin-6 in autoimmune thyroid disease is suggested.
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PMID:Interleukin-6 production by thyroid epithelial cells. Enhancement by interleukin-1. 181 93

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

Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble P-selectin, and soluble L-selectin (sL-selectin), tumor necrosis factor-alpha, and interleukin-6 were measured in patients with Graves' disease (GD) (n = 33), in patients with toxic nodular goiter (n = 34), and in a group of healthy controls (n = 36). The serum levels of sICAM-1, sVCAM-1, sE-selectin, and sL-selectin were markedly elevated in patients with GD and in patients with toxic nodular goiter before treatment with methimazole (P < 0.05 for all). After 8 weeks of therapy, serum concentrations of sVCAM-1 and sE-selectin normalized, whereas serum levels of sL-selectin and sICAM-1 remained elevated. Hormone concentrations normalized after 2 weeks, clearly preceding falling levels of circulating adhesion molecules. Serum concentrations of soluble P-selectin, TNF-alpha, and interleukin-6 did not differ among patients with GD and toxic nodular goiter and healthy subjects. Serum levels of sVCAM-1 and sICAM-1 correlated with the serum concentrations of TSH receptor antibodies (n = 33; r = 0.921 and r = 0.792, respectively) and thyroid peroxidase antibodies (n = 33; r = 0.682 and r = 0.761, respectively) but not thyroglobulin antibodies. However, no correlation between serum levels of sE-selectin, sL-selectin, and soluble P-selectin or cytokines and serum levels of thyroid peroxidase antibodies, TSH receptor antibodies, or thyroglobulin antibodies, respectively, was found. In addition, no correlation between serum levels of adhesion molecules or cytokines and thyroid hormones was seen. We conclude that both the action of thyroid hormones and the autoimmune process in GD may contribute to elevated levels of soluble adhesion molecules.
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PMID:Circulating selectins, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in hyperthyroidism. 754 2

Increased serum interleukin-6 (IL-6) concentrations have recently been reported in patients with subacute thyroiditis and in some patients with amiodarone-induced thyrotoxicosis, possibly because of cytokine release from damaged thyroid cells. In this study, serum IL-6 levels were determined by an enzyme-linked immunosorbent assay method in 18 patients given percutaneous intranodular ethanol injection (PIEI) for autonomously functioning thyroid nodule, 12 patients treated with radioactive iodine (RAI) for Graves' disease or toxic adenoma, and 23 patients submitted to fine needle aspiration (FNA) for nonfunctioning thyroid nodules. Baseline serum IL-6 levels did not differ in the 3 groups. PIEI was followed by a dramatic increase in median IL-6 values from 42 fmol/L (range, < 25 to 84) to 381 fmol/L (range, 61-9870; P < 0.0001); the peak value was attained as little as 10 min after injection. RAI was also followed by a significant (P < 0.0001) increase in IL-6 from 52 fmol/L (range, < 25 to 84) to 189 fmol/L (range, 119-1417 fmol/L); the increase after RAI was lower than that after PIEI (P < 0.05), and the peak value was attained later (after 24 h). FNA was also followed by a slight, but significant, increase in the serum IL-6 concentration from 21 fmol/L (range, < 25 to 103) to 109 fmol/L (range, < 25 to 360; P < 0.0001 vs. baseline). The increase in IL-6 was correlated with the size of nodule or goiter (P < 0.0001), but not with the amount of injected ethanol or the dose of radioiodine delivered to the thyroid. Serum thyroglobulin also increased after PIEI, RAI, or FNA, but no significant correlation could be demonstrated with the increase in IL-6. The results of this study support the concept that in the absence of nonthyroidal illnesses, which are often associated with increased serum concentrations of the cytokine, IL-6 can be regarded as a useful marker of thyroid-destructive processes.
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PMID:Interleukin-6: a marker of thyroid-destructive processes? 796 38

Stimulation of human peripheral blood monocytes with the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4) enhanced their ability to mature into cytologically and functionally characteristic veiled/dendritic cells. Veiled/dendritic cell transition induced by T3 and T4 was dependent on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in the culture, since the addition of antibodies specific for GM-CSF, TNF alpha and IL-6 to the culture system had blocking effects. The addition of antibodies to macrophage colony-stimulating factor and IL-1 had no effects. Contaminating T cells and B cells did not contribute to the transition of monocytes to veiled/dendritic cells, and it is therefore likely that the GM-CSF, TNF alpha and IL-6 produced in the culture system were derived from the monocytes themselves. Stimulation of the blood monocytes with an optimal concentration of metrizamide (14.5%), reverse T3 (rT3; 2 x 10(-10) M) or highly iodinated thyroglobulin (Tg; 2 x 10(-11) M) also resulted in an increased transition of monocytes to veiled/dendritic cells, but to a lesser extent in comparison with the thyroid hormones (T3, 31 +/- 6% and T4, 25 +/- 5% vs rT3, 22 +/- 8% and Tg with an iodination grade of 0.37%: 20 +/- 4% veiled/dendritic cells). Administration of anti-GM-CSF, anti-TNF alpha and anti-IL-6 to the culture system also had blocking effects on the transition from monocytes to veiled/dendritic cells induced by the iodinated compounds. The mechanisms by which such iodinated compounds act on the monocyte to veiled/dendritic cell transition can only be speculated on (interference H2O2-generating system?).
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PMID:Effect of thyroid hormones and other iodinated compounds on the transition of monocytes into veiled/dendritic cells: role of granulocyte-macrophage colony-stimulating factor, tumour-necrosis factor-alpha and interleukin-6. 818 78

Increased serum interleukin-6 (IL-6) concentrations have recently been reported in patients with subacute thyroiditis, possibly because of cytokine release from damaged thyroid cells. To investigate the changes in serum IL-6 concentrations in subacute thyroiditis during treatment with corticosteroid, serum IL-6 concentrations were determined by an enzyme-linked immunosorbent assay method in five patients with subacute thyroiditis. Serum IL-6 concentrations were increased moderately, and simultaneously, serum levels of T4, thyroglobulin, and C-reactive protein and erythrocyte sedimentation rate were increased markedly. The treatment with prednisolone rapidly and progressively decreased serum levels of thyroglobulin, T4, and C-reactive protein and the erythrocyte sedimentation rate. In contrast, serum IL-6 concentrations increased markedly 7 days after the treatment with prednisolone in all five patients and two of five patients showed further increases in serum IL-6 concentration on the 17th day. The rise in serum IL-6 levels in untreated patients with subacute thyroiditis in this study is compatible with previous reports. The rise in serum IL-6 levels after treatment with corticosteroid in subacute thyroiditis may reflect the dissociation between the persistent release of IL-6 from the damaged thyroid cells, immediate inhibition of secondary inflammatory reactions by corticosteroid, and the release of thyroglobulin and T4 from performed colloid stores in follicular lumen destroyed by subacute thyroiditis.
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PMID:Dissociation between serum interleukin-6 rise and other parameters of disease activity in subacute thyroiditis during treatment with corticosteroid. 863 70

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

Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells in the thyroid. There is increasing evidence that, apart from being antigen-presenting cells, they are also able to control the growth and hormone synthesis of neighbouring endocrine cells. The questions thus arise: are dendritic cells accumulating in the pre-autoimmune thyroid in response to an altered proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte chemoattractants, or both, have a role in their accumulation? We have investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid accumulation of dendritic cells--that is, at about 9 weeks of age. BB-DP rats and Wistar rats (controls) were studied from 3 to 20 weeks of age. Hyperplastic goitre development was studied by assessing the thyroid weight and by measuring the number of thyrocyte nuclei per 0.01 mm2 thyroid section. In addition, the in situ expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte-chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were studied by immunohistochemistry. The in vitro proliferative capacity of BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR) and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies consisted of measurement of the production of thyroxine (T4), triiodothyronine (T3), thyroglobulin, IL-6, TNF-alpha and MCP-1 by the thyroid follicles. BB-DP rats developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids was significantly lower than that of Wistar thyrocytes. This phenomenon also occurred in follicles isolated from BB-DP rats before hyperplastic goitre development, which produced significantly less T4, but more T3, than did Wistar follicles of the same age. At the time of and after hyperplastic goitre development, BB-DP follicles exhibited altered metabolic behaviour and produced significantly more T4, but equal amounts of T3 compared with both Wistar follicles of the same age and follicles of younger BB-DP rats (both under basal conditions and TSH-stimulated). In vitro IL-6 production by these BB-DP thyroid follicles was also increased. There was no noteworthy difference in production of thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-alpha was not produced by BB-DP or Wistar thyroid follicles. Immunohistochemistry revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells at all times of sampling. MCP-1 and TNF-alpha were expressed only when infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages > 18 weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB-DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1 expression was found on blood vessels and leucocytes in these infiltrations. At the time of intrathyroidal dendritic cells accumulation, BB-DP rats develop a small hyperplastic goitre. At that time there is also in vitro evidence for a shift to a higher production of thyroxine and IL-6 from thyrocyte follicles. The in vitro proliferation rate of BB-DP thyrocytes is, however, abnormally low (both in the pre- and hyperplastic period). Similar pre-autoimmune thyroid growth abnormalities have been described in another animal model of thyroid autoimmune disease, the obese strain chicken.
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PMID:Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response. 961 56

A new human thyroid carcinoma cell line, KTC-1, was established from the malignant pleural effusion of a recurrent thyroid carcinoma patient. Cytogenetic analysis revealed a normal karyotype, and no p53 mutation in exons 5-9 was detected. This cell line is tumorigenic in athymic nude mice. Histological findings by light and electron microscopy, such as the absence of follicular structures and the existence of intranuclear cytoplasmic inclusions and psammoma bodies, indicated transplanted tumors to be a poorly differentiated papillary thyroid carcinoma. A low expression level of thyroglobulin was detected by immunocytochemistry and RT-PCR. Messenger ribonucleic acid (mRNA) expression of thyroid transcription factor-1 and PAX-8 was also detected. No mRNA expression of TSH receptors, thyroid peroxidase, or Na+/I- symporter was detected. Interleukin-6 and leukemia inhibitory factor were secreted into the medium. These findings suggest this cell line to be functionally poorly differentiated. Moreover, all-trans-retinoic acid increased the mRNA expression of thyroglobulin and decreased both the mRNA expression and secretion of interleukin-6 and leukemia inhibitory factor while significantly stimulating growth. RT-PCR analysis of retinoic acid receptors (RARs) revealed that KTC-1 cells express a moderate level of RARalpha and -gamma, but a low level of RARbeta. This cell line may be useful for studying redifferentiation therapy for thyroid carcinoma.
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PMID:All-trans-retinoic acid modulates expression levels of thyroglobulin and cytokines in a new human poorly differentiated papillary thyroid carcinoma cell line, KTC-1. 1094 99

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.
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PMID:Serum levels of the cytokines IL-1beta, IL-6 and ICAM-1 after 131I-treatment of Graves' disease and nodular goiter. 1096 35


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