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)

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

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

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

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

Interleukin-6 (IL-6) is the main mediator of the acute phase response. Increased serum concentrations of the cytokine have been found in patients with nonthyroidal inflammatory disorders and infections. In 18 patients with subacute thyroiditis (SAT) evaluated within 1-2 weeks after the onset of the disease, serum IL-6 values, as assessed by an ELISA method having a limit of detection of 25 fmol/L, ranged 139.2-543.9 fmol/L (mean +/- SE, 287.2 +/- 28.2 fmol/L). These values were significantly higher than those of 25 normal healthy controls (mean +/- SE, 26.2 +/- 5.5 fmol/L, range < 25-99.4), 18 of whom had serum IL-6 values below the detection limit. The increase in serum IL-6 levels in SAT patients appeared to be related to the inflammatory disorder and not to thyrotoxicosis, because 18 Graves' disease patients and 13 patients with toxic adenoma or toxic multinodular goiter had significantly lower serum IL-6 concentrations (101.7 +/- 35.2 fmol/L, range < 25-251, for Graves' disease, 79.6 +/- 41.4 fmol/L, range < 25-168.5, for toxic adenoma, p < 0.001 vs SAT for both groups) despite the markedly higher levels of total and free thyroid hormones. Neither free T4 nor free T3 values were correlated with serum IL-6 levels both in SAT and Graves' patients. Twelve SAT patients were reevaluated 3-4 months later, after remission of the disease and at least one month after glucocorticoid withdrawal. At the final observation, all SAT patients showed a normalization of IL-6 concentration, which was undetectable in 8/12 (mean +/- SE, 22.8 +/- 5.4 fmol/L, p < 0.001 vs acute phase values).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased serum interleukin-6 concentration in patients with subacute thyroiditis: relationship with concomitant changes in serum T4-binding globulin concentration. 851 77

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

Increased serum interleukin-6 (IL-6) concentrations have been reported in patients with thyroid destructive processes. In the present study we measured IL-6 and soluble IL-6 receptor (sIL-6R) concentrations in the serum of normal subjects and patients with Graves' disease using a high sensitivity sandwich enzyme-linked immunoassay. We found increased serum IL-6 and sIL-6R concentrations (69.3 fmol/L, and 964 pmol/L, respectively) in 49 hyperthyroid patients with Graves' disease (GD) compared to those in controls [55.8 fmol/L (P = 0.019) and 772 pmol/L (P = 0.007), respectively]. In 31 newly diagnosed GD patients, serum concentrations of IL-6 and sIL-6R during the hyperthyroid phase were elevated, and after therapy with methimazole only, serum sIL-6R concentrations returned to normal (940 vs. 726 pmol/L; P < 0.001) but serum IL-6 did not. Serum sIL-6R concentrations (mean +/- 2 SD) were higher in GD patients with active inflammatory thyroid-associated ophthalmopathy than those in patients with inactive or absent thyroid-associated ophthalmopathy (P < 0.05). In conclusion, we have demonstrated activation of the IL-6 system in GD and, for the first time, have measured and found increased serum sIL-6R concentrations in hyperthyroid GD patients.
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PMID:Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves' disease. 910 Jun 15

Interleukin-6 (IL-6), a pleiotropic cytokine, is postulated to be involved in the pathogenesis of sick euthyroid syndrome, although the direct in vitro effects of IL-6 on human thyroid function are controversial. Because IL-6 signal can be transduced when the complex of IL-6 and soluble IL-6 receptor (sIL-6R) binds to gp 130, an IL-6 signal transducer, we studied the effects of IL-6 and sIL-6R on thyroid function, using human thyroid follicles obtained from patients with Graves' disease. IL-6 alone had no inhibitory effect on TSH-induced thyroid function (125I incorporation and organic 125I release), even at supraphysiological concentrations. However, in the presence of physiological concentrations of sIL-6R (100 ng/ml), IL-6 inhibited thyroid function dose dependently and completely, accompanied with the decreased ratio of 125I-T3/125I-T4 not only in the thyroid follicles but also in the culture medium. Thyroid follicles did not secrete sIL-6R but produced IL-6 constitutively. Consistent with these findings, sIL-6R inhibited thyroid function slightly at high concentrations. Furthermore, RT-PCR analyses revealed that human thyroid follicles expressed the messenger RNAs for IL-6 and gp130 but scarcely messenger RNA for IL-6R. These in vitro findings suggest that IL-6 alone hardly affects thyroid function in thyroid follicles in which IL-6R gene is scarcely expressed. However, because sIL-6R is present abundantly in serum, IL-6 in vivo would be capable of inhibiting the synthesis and release of T4 and, to a greater extent, T3 from the thyroid gland. These in vitro findings are at least partly related to the development of sick euthyroid syndrome.
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PMID:Interleukin-6 (IL-6) inhibits thyroid function in the presence of soluble IL-6 receptor in cultured human thyroid follicles. 889 57

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


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