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)

Since serum concentrations of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) are elevated in infectious and inflammatory illnesses, we examined their potential role in contributing to the low TSH concentrations associated with such conditions, both at the level of the pituitary and the hypothalamus. 20 hours exposure to recombinant murine TNF-alpha (10(-11) to 10(-10) mol/l) enhanced the basal and the TRH-stimulated release of TSH by cultured rat anterior pituitary cells, but 4 hours exposure increased only basal TSH secretion. Recombinant human (rh) IL-1 beta, at a dose of 10(-11) mol/l only, produced a very small increase in basal TSH secretion after 4h, but not 20h, exposure. TRH-stimulated TSH secretion was not affected by IL-1 beta in concentrations up to 10(-10) mol/l, at either exposure time. Rh IL-6 (10(-12) to 10(-9) mol/l), had no effect on basal or TRH-stimulated TSH secretion at either exposure time. TNF-alpha, IL-1 beta, and IL-6 all failed to modify the inhibitory response to triiodothyronine (T3) and thyroxine (T4) on TSH secretion, under basal or TRH-stimulated conditions. Indirect effects of the cytokines on the stimulation or inhibition of TSH secretion, via TRH or SRIF respectively, were tested in isolated rat hypothalamic slices. 30 min exposure to TNF-alpha, IL-1 beta, or IL-6 had no effect on the basal release of SRIF. However, IL-1 beta, from 2.5 x 10(-12) to 10(-10) mol/l, produced a dose-dependent enhancement of the SRIF released by 5 x 10(-2) mol/l extracellular K+. The effect appeared to be mediated via IL-1 receptors, and to involve prostanoid formation, since it was inhibited by IL-1 receptor antagonist protein, 10(-7) mol/l, and indomethacin, 2.8 x 10(-5) mol/l, respectively. Neither basal nor K(+)-stimulated TRH release was influenced by TNF-alpha, IL-1 beta, or IL-6. The results indicate that direct effects of these cytokines on the pituitary do not contribute to reduced circulating TSH concentrations during inflammation and infection, but that enhanced hypothalamic release of SRIF, in response to elevated IL-1 beta, could contribute to such a decrease in TSH. None of the cytokines tested decreased hypothalamic TRH release in vitro. However, further in vivo experiments would be required to determine whether a longer exposure to these agents could reduce TRH release either directly, or indirectly via inputs from outside the hypothalamus.
 ...
PMID:Effect of interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 on the control of thyrotropin secretion. 762 15

Using a functioning rat thyroid cell line (FRTL-5), we studied the effects of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) on thyroidal type I iodothyronine 5'-deiodination (I-5'-deiodination) and on the expression of I-5'-deiodinase (I-5'-D) mRNA. After 24 h incubation in medium containing 0.5 microM rT3 with a tracer amount of [125I]rT3, radioactivity of released 125I- was counted. Deiodination in live FRTL-5 cells was enhanced about three times from the basal level by the addition of TSH and was inhibited markedly by propylthiouracil and dose dependently by T4. These results suggest the suitability of this model for investigating I-5'-deiodination in live thyroid tissue. Basal and TSH-induced I-5'-deiodination were significantly inhibited by 100 ng/liter of IL-1 beta and IL-6, and the inhibitory effect of TNF-alpha was seen over 1 microgram/liter. I-5'-deiodination was restored by removal of the cytokines. TSH-induced cAMP production and (Bu)2cAMP-induced I-5'-deiodination were also inhibited by the cytokines. Catalase, dexamethasone, and indomethacin did not abolish the inhibitory effects of the cytokines. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a marked suppression of I-5'-D mRNA expression by IL-1 beta and IL-6. We conclude that these cytokines inhibit the thyroidal type I I-5'-deiodination in the order of potency IL-1 beta > IL-6 >> TNF-alpha, probably by decreasing the I-5'-D mRNA level.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 on type I iodothyronine 5'-deiodination in rat thyroid cell line, FRTL-5. 762 12

Interleukin-2 (IL-2) is a pluripotential cytokine that, besides its role in the regulation of immunocompetent cells function, also stimulates hormone secretion. On the other hand, several factors, including cytokines (interleukin-1, IL-1; interleukin-6, IL-6) and pituitary hormones (thyrotropin, TSH; prolactin, PRL), exert stimulatory effects on T-cell connected IL-2 production. In order to evaluate the role of both pituitary hormones in the activation of the immune system, the following two standard diagnostic tests were performed: TRH test (0.2 mg) in 8 healthy human subjects (4F/4M) aged 18-50 years, and oral metoclopramide (MCP) test (10 mg) in 8 females with galactorrhea and regular menstruation aged 18-52 years. The mobilization (peak response) of PRL, TSH, triiodothyronine (T3), thyroxin (T4), IL-1 beta, IL-2, IL-6 in TRH test, and PRL, IL-1 beta, IL-2, IL-6 for MCP test were evaluated. The responses of TSH (2.0 +/- 0.3 vs 12.3 +/- 2.2 microlU/ml, p < 0.01), PRL (15.3 +/- 2.3 vs 46.4 +/- 8.8 ng/ml, p < 0.01), T3 (178.0 +/- 16.4 vs 248.7 +/- 21.1 ng/dl, p < 0.001), T4 (7.9 +/- 0.4 vs 9.6 +/- 0.5 micrograms/dl, p < 0.001), and IL-2 (45.6 +/- 7.8 vs 79.9 +/- 16.4 fmol/ml, p < 0.05) in TRH test were noted. The peak response of PRL (16.3 +2- 2.6 vs 107.7 +/- 22.4 ng/ml, p < 0.01) in MCP test was also observed, but without any changes in interleukin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Increased interleukin-2 levels during standard TRH test in man. 781 86

Variations in the serum concentration of interleukin-6 (IL-6) have been reported concomitantly with thyroid dysfunction: increased serum IL-6 levels have been found in patients with thyroidal destructive processes, such as subacute thyroiditis, some forms of amiodarone-induced thyrotoxicosis, or after percutaneous ethanol injection into "hot" thyroid nodules, as a result of the cytokine release from the damaged thyrocyte. In addition, recent in vitro evidence suggests that IL-6 might account, at least in part, for changes of thyroid economy found in nonthyroidal illness (NTI). In this cross-sectional study we addressed this problem by measuring serum IL-6 levels in 71 patients with NTI, due to neoplasia (n = 25), chronic liver disease (n = 9), chronic renal failure (n = 28), or other chronic nonthyroidal disorders (n = 9). These patients had reduced mean serum total T3 (TT3) and free T3 (FT3) concentrations, normal total and free T4 levels, normal TSH values, and increased serum reverse T3 (rT3) concentration (with the exception of chronic renal failure patients, who had normal rT3 levels). Serum IL-6 concentration was increased above normal (i.e. > 100 fmol/L) in almost all NTI patients, especially in those with low T3 values (median value: 258 fmol/L, range 73-3210, vs 152 fmol/L, range < 12.5-460, in patients with normal TT3 values, p < 0.001). Serum IL-6 values in NTI patients were negatively correlated with serum FT3 values (r = 0.56, p < 0.001), and positively correlated with serum rT3 values (r = 0.78, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Relationship of the increased serum interleukin-6 concentration to changes of thyroid function in nonthyroidal illness. 793 Mar 79

Combination of TSH and Interleukin-6 (IL-6) can stimulate DNA synthesis in FRTL-5 cells. Phorbol 12-myristate 13-acetate (PMA) stimulates G0 to G1 transition but inhibits G1 to S transition in these cells. We studied the effect of IL-6 on DNA synthesis in TSH-pretreated FRTL-5 cells in the presence or absence of PMA. IL-6 induced DNA synthesis when it was added to TSH-pretreated cells. Further, PMA inhibited the DNA synthesis induced by IL-6. These data might suggest that in FRTL-5 cells IL-6 can show its mitogenic effect in G1 phase of their cell cycle progression.
 ...
PMID:Phorbol ester inhibits DNA synthesis induced by interleukin-6 in TSH-pretreated FRTL-5 cells. 805 33

We studied the effects of interleukin-6(IL-6) on DNA synthesis and cyclic AMP production in rat thyroid FRTL-5 cells. When cells were incubated with IL-6 in the presence or absence of IGF-I, cell proliferation was not observed. By contrast, IL-6 stimulated DNA synthesis in a dose dependent manner when TSH was added concomitantly. On the other hand, IL-6 did not modulate the cAMP accumulation in the presence or absence of TSH. These data demonstrate that, like IGF-I, IL-6 may be able to act as a growth factor through activation of a mitogenic signal transduction pathway different from A-kinase in FRTL-5 cells.
 ...
PMID:Effect of interleukin-6 on cell proliferation of FRTL-5 cells. 838 10

It has been suggested that the thyroid itself may contribute to the inflammatory process observed in autoimmune thyroiditis by releasing the cytokines interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), but studies of cytokine gene expression in thyrocytes have been limited and conflicting. A semi-quantitative reverse transcription-PCR technique has been used to investigate the expression of IL-1 alpha, IL-6 and IL-8 mRNA in the human thyroid cell line HTori3 and in cultures of primary human thyroid follicular cells (TFCs). Cytokine mRNA levels were examined over a 24-h period, and the modulatory effects of exogenous IL-1 alpha, interferon-gamma (IFN-gamma) and TSH investigated. Basal expression of IL-1 alpha, IL-6 and IL-8 mRNA was detected in HTori3 and primary TFC cultures. Stimulation with IL-1 (10 U/ml) for 12 h produced an increase in the level of IL-1 alpha mRNA in both primary TFC and HTori3 cultures. IL-6 and IL-8 mRNA levels were increased by the addition of IL-1 in both cell types, and this effect was detected throughout the 24-h time-course. IFN-gamma (100 U/ml) had no significant effect on cytokine gene expression. A higher concentration of IFN-gamma (500 U/ml) had no significant effect on the expression of IL-1 alpha or IL-8 but produced an increase in the level of IL-6 mRNA in primary cultures and in HTori3 cells. Addition of TSH (1 mU/ml) produced an increase in the level of IL-1 alpha mRNA in primary TFC and HTori3 cells, at 12 and 24 h. TSH had no significant effect on the expression of IL-6 or IL-8 mRNA. These results demonstrate that human TFCs constitutively express IL-1 alpha, IL-6 and IL-8 mRNA and that this expression can be modulated by IL-1, IFN-gamma and TSH.
 ...
PMID:Semi-quantitative analysis of interleukin-1 alpha, interleukin-6 and interleukin-8 mRNA expression by human thyrocytes. 854 10

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.
 ...
PMID:Interleukin-6 (IL-6) inhibits thyroid function in the presence of soluble IL-6 receptor in cultured human thyroid follicles. 889 57

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.
 ...
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

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


<< Previous 1 2 3 4 Next >>