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)

We studied a wide variety of surgical patients to determine whether serum levels of interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) correlate with the changes in serum thyroid hormone levels of the postoperative period. Surgical procedures were divided into minor surgery (cholecystectomy, n = 12), moderate surgery (colorectal cancer and stomach cancer, n = 54), and extensive surgery (esophageal cancer or pancreatic cancer, n = 6). One day after surgery, serum free T3 levels decreased in all 3 groups when compared to the preoperative values; serum free T4 levels did not change regardless of surgical procedure. Serum TSH levels decreased significantly 1 day after surgery in the groups of moderate and extensive surgery. Serum levels of IL-6 increased 12 h after surgery and began to decrease gradually thereafter. There was no change in serum levels of TNF-alpha before and after surgery. The increment of serum IL-6 was dependent on the surgical procedures: the more extensive the surgery, the greater the increase in serum IL-6. Serum free T3 and free T4 levels were inversely correlated with the serum levels of IL-6. To further examine whether IL-6 is responsible for alteration of thyroid hormone production, cultured porcine thyroid follicles were exposed to 0 to 20 ng/ml of recombinant human IL-6 for 24 to 48 h. Then, type 1 5'-deiodinase activity (T4 to T3 converting enzyme), iodide uptake, and thyroid peroxidase (TPO) activity were measured. Our in vitro experiments showed no effect of IL-6 on these parameters. In summary, surgical procedure can cause elevation of serum IL-6 and decrease in serum free T3 levels. However, IL-6 alone does not appear to be a strong candidate for alteration of thyroid hormone production including T3 generation from T4.
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PMID:Elevated serum interleukin-6 and decreased thyroid hormone levels in postoperative patients and effects of IL-6 on thyroid cell function in vitro. 900 Nov 95

Administration of tumour necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) to animals and humans results in changes in circulating thyroid hormone concentrations similar to those seen in non-thyroidal illness (NTI). Inflammatory cytokines have been postulated as mediators of the euthyroid sick syndrome by inhibiting type 1 5'-deiodinase (5'D-I) enzyme activity. We have investigated direct effects of cytokines upon 5'D-I expression, measuring changes in 5'D-I enzyme activity and mRNA in phi1 rat liver cells. All three cytokines stimulated 5'D-I enzyme activity: TNF alpha 326 +/- 43% (100% in controls, mean + S.E.M., n = 9, P < 0.01 by ANOVA), IL-1beta 297 +/- 8% and IL-6 272 +/- 25%. Co-incubation with cycloheximide abolished stimulation by each cytokine. Kinetic analysis revealed that stimulation of 5'D-I enzyme activity was a result of significantly increased Vmax, (P < 0.01 by ANOVA) with Km relatively unchanged. 5'D-I mRNA abundance was not significantly changed following treatment by any of the three cytokines. These findings do not support the hypothesis that inflammatory cytokines may mediate the euthyroid sick syndrome by causing inhibition of 5'D-I activity.
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PMID:Inflammatory cytokines and type I 5'-deiodinase expression in phi1 rat liver cells. 920 2

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.
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PMID:Color flow Doppler sonography rapidly differentiates type I and type II amiodarone-induced thyrotoxicosis. 929 40

Interleukin-6 (IL6) is believed to be involved in alterations of thyroid hormone metabolism in acute nonthyroidal illness. To evaluate the effects of IL6 on thyroid hormone metabolism in a chronic IL6-mediated disease, we measured thyroid hormone concentrations in multiple myeloma patients treated with intravenous anti-IL6 chimeric monoclonal antibodies ([cMabs] Kd = 6.25 x 10(-12) mol/L). Twelve patients were studied, receiving at least one complete treatment cycle of 14 days (daily dose: 5 mg, n = 3; 10 mg, n = 3; 20 mg, n = 3; and 40 mg, n = 3). Eight of them also completed a second treatment cycle of 14 days. Thyroid hormone concentrations were measured before, during, and after treatment with the anti-IL6 cMab. Even in the group with the lowest dosage, IL6 activity measured by the B9 bioassay was blocked completely. Compared with the reference ranges, 10 of 12 patients had one or more abnormal pretreatment values for thyroid hormone concentrations. Thyroid autoantibodies were negative in all patients. There was no correlation between thyroid hormone concentrations and IL6 levels, although plasma IL6 levels were increased in all but one subject. Moreover, neutralization of free IL6 by the anti-IL6 cMab did not affect thyroid hormone concentrations, although IL6-dependent C-reactive protein (CRP) levels decreased to undetectable levels in 11 of 12 patients. Two patients developed infectious complications resulting in increased free IL6 and CRP levels and in profound alterations of thyroid hormone levels consistent with an acute euthyroid sick syndrome. We conclude that IL6 is not a major determinant of thyroid hormone abnormalities in a chronic disease like multiple myeloma, but IL6 may be involved in thyroid hormone metabolism in acute diseases (probably in combination with other factors).
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PMID:Modulation of chronic excessive interleukin-6 production in multiple myeloma does not affect thyroid hormone concentrations. 936 97

Interleukin-6 (IL-6) is produced in response to inflammatory and noninflammatory stress and acts as the principal regulator of the acute-phase protein response. IL-6 stimulates the hypothalamic-pituitary-adrenal axis and may be involved in the thyroid function abnormalities observed in nonthyroidal illness (NTI). This study examined the effects of single-dose IL-6 (3 microg/kg subcutaneously [s.c.]) in healthy human subjects: 19 received IL-6 and 13 received control saline injection. The dose of IL-6 was chosen on the basis of previous studies indicating that the peak IL-6 level after injection reaches concentrations observed with major stress such as abdominal surgery. Plasma levels of thyrotropin (TSH), free thyroxine (FT4), total T4, 3,5-3'-L-triiodothyronine (T3), 3,3'-5'-L-triiodothyronine or reverse T3 (rT3), and thyroxine-binding globulin (TBG) were measured over a 4-hour period and 24 hours after IL-6 injection. Plasma TSH levels were 27% lower 240 minutes after IL-6 relative to control levels (0.93 +/- 0.10 v 1.28 +/- 0.18 mIU/mL, P = .001), but recovered by 24 hours. Plasma FT4 was elevated at 240 minutes compared with the controls (1.16 +/- 0.04 v 1.03 +/- 0.03 ng/dL, P = .0002). T4 levels were also elevated at 240 minutes (7.8 +/- 0.36 v 7.05 +/- 0.37 microg/dL, P = .0003). TBG levels were not significantly changed at this time point. At 24 hours, T3 levels were 19% lower than the control values (87.6 +/- 5.1 v 108.5 +/- 5.4 ng/dL, P = .0002); plasma rT3 levels were elevated by 21% compared with control levels (30.6 +/- 1.7 v 24.3 +/- 1.3 ng/dL, P = .002), while FT4 levels returned to normal. The changes in T3/rT3 levels were reminiscent of the pattern observed in NTI that may be due to inhibition of type-1 5'-deiodinase. Cortisol levels were greatly elevated after IL-6 compared with control values; peak levels were observed 120 minutes after IL-6 injection (28.7 +/- 1.6 v 9.5 +/- 1.0 ng/dL, P < .0001). This elevation in cortisol may have contributed to the suppression of TSH levels and inhibition of type-1 5'-deiodinase activity. Alternatively, IL-6 may have suppressed TSH secretion via a direct suprapituitary action. The elevation of T4 and FT4 levels may have been due to inhibition of T4 degradation at the liver and/or by direct action of IL-6 on the thyroid gland. These findings demonstrate the potent effects of IL-6 on thyroid hormone metabolism in healthy individuals, and suggest that IL-6 may act directly or indirectly at two or more sites on thyroid hormone secretion and metabolism.
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PMID:Acute and delayed effects of a single-dose injection of interleukin-6 on thyroid function in healthy humans. 978 36

It is well known that excessive thyroid hormone in the body is associated with bone loss. However, the mechanism by which thyroid hormone affects bone turnover remains unclear. It has been shown that it stimulates osteoclastic bone resorption indirectly via unknown mediators secreted by osteoblasts. To determine if interleukin-6 (IL-6) or interleukin-11 (IL-11) could be the mediator(s) of thyroid hormone-induced bone loss, we studied the effects of 3,5,3'-tri-iodothyronine (T3) on basal and interleukin-1 (IL-1)-stimulated IL-6/IL-11 production in primary cultured human bone marrow stromal cells. T3 at 10(-12)-10(-8) M concentration significantly increased basal IL-6 production in a dose-dependent manner. It also had an additive effect on IL-1-stimulated IL-6 production, but failed to elicit a detectable effect on basal or IL-1-stimulated IL-11 production. Treatment with 17beta-estradiol (10(-8) M) did not affect the action of T3 on IL-6/IL-11 production. These results suggest that thyroid hormone may stimulate bone resorption by increasing basal and IL-1-induced IL-6 production from osteoblast-lineage cells, and these effects are independent of estrogen status.
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PMID:Thyroid hormone stimulates basal and interleukin (IL)-1-induced IL-6 production in human bone marrow stromal cells: a possible mediator of thyroid hormone-induced bone loss. 985 81

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.
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PMID:Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients. 1009 8

We investigated the effects of the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) on 3,3', 5-triiodo-L-thyronine, or thyroid hormone (T(3))-stimulated sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) gene expression on cultured neonatal rat cardiac myocytes. A reduction of T(3) induced increases in SERCA2 mRNA levels after co-treatment with LIF or IL-6. To investigate for the molecular mechanism(s) responsible for the blunted gene expression, a 3.2-kb SERCA2 promoter construct containing a reporter gene was transfected into cardiac myocytes. T(3) treatment stimulated transcriptional activity twofold, whereas co-treatment with T(3) and either of the cytokines caused an inhibition of T(3)-induced SERCA2 transcriptional activity. A T(3)-responsive 0.6-kb SERCA2 construct also showed a similar inhibition by cytokines. Cytokine inhibition of SERCA2 transcriptional activity was also evident when a 0.6-kb SERCA2 mutant, T(3)-unresponsive promoter construct was used. Treatment with T(3) and cytokines showed a significant decrease in transcription when a reporter construct was used that was comprised of direct repeats of SERCA2 thyroid response element I. These data provide evidence for cytokine-mediated inhibitory effects on the SERCA2 promoter that may be mediated by interfering with T(3) action.
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PMID:Thyroid hormone-induced stimulation of the sarcoplasmic reticulum Ca(2+) ATPase gene is inhibited by LIF and IL-6. 1075 Dec 9

The euthyroid sick syndrome is reported to exist in acute myocardial infarction(AMI). Previous reports showed serum levels of triiodothyronine(T3) are low and thyroid stimulating hormone(TSH) is normal or subnormal levels in patients with AMI. However, the mechanism of altered thyroid hormone metabolism is unknown. Interleukin-6(IL-6) is reported to be a key role in the pathogenesis of AMI and euthyroid sick syndrome. We measured circulating TSH, free T3(FT3), free thyroxine (FT4), IL-6, soluble IL-6 receptor, soluble transducing 130-kD glycoprotein, atrial natriuretic peptide(ANP) and brain natriuretic peptide in 25 patients and 32 healthy subjects. Circulating FT3 levels in patients with AMI became lower than in control group(p < 0.05). IL-6 levels were significantly(p < 0.05) higher than those of healthy subjects. The peak levels of IL-6 was 30.5 +/- 46.9 pg/ml at 25-27 hours(the first peak) and 64.4 +/- 24.6 pg/ml at 70-72 hours(the second peak). FT3 was negatively related to IL-6(p < 0.05) and hANP(p < 0.05) in patients with AMI. These results indicate that the lower levels of FT3 show the greater severity of AMI. We conclude that euthyroid sick syndrome occurs in patients with AMI and euthyroid sick syndrome may regulated by IL-6 through suppressed of thyroid function.
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PMID:[Studies on circulating interleukin-6 and thyroid functions in acute myocardial infarction]. 1080 37

We report the case of a 55-year-old woman who presented with hypercortisolism secondary to ectopic adrenocorticotrophic hormone secretion and severe non-thyroidal illness syndrome (NTIS) due to metastatic small cell lung carcinoma associated with severe infections. The patient initially showed hormonal profiles of pituitary hypothyroidism and gonadal hypofunction. After decrease in cortisol production following treatment with chemotherapy and metyrapone, serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations normalized. Study of the relative contributions of cortisol and pro-inflammatory cytokines (interleukin-6 and tumour necrosis factor alpha) to the overall variability in thyroid function tests disclosed a significant and independent effect of serum cortisol on serum TSH concentrations; the variability in free thyroid hormone concentration was explained only by changes in TSH concentration. These observations indicate that cortisol could be the major determinant of changes in serum TSH concentrations in clinical conditions accompanied by hypercortisolism, as occurs in NTIS.
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PMID:Transient pituitary hypothyroidism in a patient with ectopic adrenocorticotrophic hormone secretion. 1081 42


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