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 coexistence of pheochromocytoma and primary adrenal Cushing's syndrome of the same adrenal gland has rarely been reported. We describe here the case of a female patient presenting with mild Cushing's stigmata, hypertension and diabetes mellitus in whom we diagnosed a pheochromocytoma of the left adrenal gland with coexisting non-ACTH-dependent cortisol hypersecretion. While hormonal work-up was still in progress, the patient became pregnant and wanted to carry her pregnancy to full-term. A laparoscopic adrenalectomy in the 17th week of gestation was decided upon and the patient accordingly prepared for surgery by pre-treatment with phenoxybenzamine. Successful surgery--the first ever reported laparoscopic resection of a pheochromocytoma in pregnancy--without perioperative complications was performed under general anesthesia, with the patient receiving peri- and post-operative hydrocortisone substitution. Pathohistological examination revealed a pheochromocytoma with positive immunostaining for interleukin-6 (IL-6) and negative immunostaining for ACTH, vasoactive intestinal polypeptide (VIP) and cytochrome P450, and with no signs of malignancy. A paracrine stimulation of the ipsilateral adrenal cortex by IL-6 produced by the pheochromocytoma, leading to cortical hyperplasia and subclinical Cushing's syndrome, is suggested by the positive immunostaining for IL-6 and the MRI findings. Post-operatively, secondary adrenal insufficiency ensued, necessitating continuing hydrocortisone replacement over 12 months. Hypertension resolved after surgery, and diabetes after the uncomplicated vaginal delivery at term.
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PMID:Pheochromocytoma and sub-clinical Cushing's syndrome during pregnancy: diagnosis, medical pre-treatment and cure by laparoscopic unilateral adrenalectomy. 1047 54

Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), powerful stimulants of the hypothalamic-pituitary-adrenal (HPA) axis, increase in response to whole body exercise. Strenuous inspiratory resistive breathing (IRB), a form of clinically relevant "exercise" for the respiratory muscles, produces beta-endorphin through a largely unknown mechanism. We investigated (in 11 healthy humans) whether strenuous IRB produces proinflammatory cytokines and beta-endorphin in parallel with stimulation of the HPA axis, assessed by concurrent measurement of ACTH. Subjects underwent either severe [at 75% of maximal inspiratory pressure (P(m) (max))] or moderate (at 35% of P(m) (max)) IRB. Plasma cytokines, beta-endorphin, and ACTH were measured at rest (point R), at the point at which the resistive load could not be sustained (point F), and at exhaustion [15 min later (point E)]. During severe IRB, IL-1beta increased from 0.83 +/- 0.12 pg/ml at point R to 1.88 +/- 0. 53 and 4.06 +/- 1.27 pg/ml at points F and E, respectively (P < 0. 01). IL-6 increased from 5.30 +/- 1.02 to 10.33 +/- 2.14 and 11.66 +/- 2.29 pg/ml at points F and E, respectively (P = 0.02). ACTH and beta-endorphin fluctuated from 20.87 +/- 5.49 and 25.03 +/- 3.97 pg/ml at point R to 22.97 +/- 4.41 and 26.32 +/- 3.93 pg/ml, respectively, at point F and increased to 46.96 +/- 8.55 and 40.32 +/- 5.94 pg/ml, respectively, at point E (P < 0.01, point E vs. point F). There was a positive correlation between the IL-6 at point F and the ACTH and beta-endorphin at point E (r = 0.88 and 0.94, respectively; P < 0.01) as well as between the increase in IL-6 (between points R and F) and the increases in ACTH and beta-endorphin (between points F and E, r = 0.91 and 0.92, respectively; P < 0.01). Moderate IRB did not produce any change. We conclude that severe IRB produces proinflammatory cytokines and stimulates the HPA axis in humans secondary to the production of cytokines (especially IL-6).
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PMID:Strenuous resistive breathing induces proinflammatory cytokines and stimulates the HPA axis in humans. 1051 39

The purpose of this work was to compare the plasma adrenocorticotropin (ACTH), corticosterone and interleukin-6 (IL-6) responses that rats of the outbred Sprague-Dawley strain obtained from two different vendors: Charles River (CR) and Harlan (HSD). Basal plasma ACTH and IL-6 concentrations were similar in rats from either vendor (HSD or CR), while CR animals exhibited slightly elevated corticosterone levels in late afternoon. Inflammatory stimuli such as lipopolysaccharide (LPS) (1 microgram/kg, i.v.) or turpentine (50 microliter/100 g, i.m.) which induce the production of endogenous cytokines, produced a significantly larger ACTH response in CR, compared to HSD rats, while the overall corticosterone responses were comparable in both rat groups. This could probably not be accounted for by a greater ACTH responsiveness in CR rats per se because CR and HSD rats showed similar peak ACTH responses to electrofootshock. Furthermore, in contrast to when the stimulus was one that induced endogenous cytokine production, the administration of exogenous interleukin-1beta (IL-1beta, 200 ng/kg, i.v.) produced a 2-fold greater rise in plasma ACTH concentrations in HSD rats compared to CR rats. The plasma IL-6 responses to the inflammatory stimuli showed a similar pattern to ACTH, with LPS and turpentine tending to pruduce greater IL-6 responses in CR rats, though these differences were not statistically significant. In contrast HSD rats had a significantly greater IL-6 response to IL-1beta than did CR rats. Collectively, these results show that Sprague-Dawley rats obtained from different commercial sources can differ in immune-neuroendocrine responses to inflammatory stimuli.
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PMID:Sprague-Dawley rats obtained from different vendors exhibit distinct adrenocorticotropin responses to inflammatory stimuli. 1051 81

We have previously observed significant, albeit decreased, corticosterone responses to restraint stress in corticotropin releasing hormone (CRH)-deficient (knockout, CRH KO) mice. Because different stressors have been shown to engage different populations of hypophysiotropic neurons, we have used hypoglycemia and hypovolemia to test whether CRH-independent pituitary-adrenal activation is evoked by stimuli other than restraint. Insulin injection in fasted CRH KO mice elicited increases in corticosterone that were markedly lower than those in wild type but marginally significant relative to corresponding KO controls. Consistent with impaired adrenocortical function, hypoglycemia-induced epinephrine secretion was reduced in female CRH KO mice. Hypovolemia produced by retro-orbital bleeding also significantly elevated corticosterone in CRH KO mice. In contrast to significant stress-induced increases in corticotropin (ACTH) in wild-type mice, those in CRH KO mice were slight, transient and difficult to detect without frequent sampling. Restraint-induced interleukin-6 (IL-6) levels were similar between wild-type and CRH KO mice, arguing against compensatory changes in IL-6 responses to restraint due to CRH deficiency. CRH infusion enhanced adrenocortical responses to restraint independently of effects on basal corticosterone levels, suggesting that pituitary-adrenal activity is augmented by factors besides CRH during stress. We conclude that although stress-induced pituitary-adrenal activity does not require acute increases in CRH, CRH is required to support the normal amplitude of adrenocortical axis responsiveness to other endocrine or neural factors during stress.
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PMID:CRH deficiency impairs but does not block pituitary-adrenal responses to diverse stressors. 1068 22

Several interleukins have been reported to play a major role in the regulation of steroid secretion at all three levels of the hypothalamic-pituitary-adrenal axis. The objective of this study was to investigate the effect of interleukin-3 (IL-3) and interleukin-6 (IL-6) on cortisol secretion of bovine adrenocortical cells in primary culture under serum-free conditions. Both IL-3 and IL-6 stimulated basal cortisol secretion dose-dependently to a similar extent at a similar time course. After incubation with IL-3 or IL-6 at concentrations of 100 microg/l, a maximum 4.1-fold increase of the cortisol secretion was reached after 12 h (P<0.01). Coincubation of IL-3 and IL-6 (100 microg/l) revealed no significant synergism. To elucidate a possible involvement of arachidonic acid metabolites in the signal transduction, we coincubated IL-3 or IL-6 together with the cyclo-oxygenase inhibitor indometacin or the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Coincubation with indometacin completely abolished the stimulatory effect of IL-6 but had no effect on IL-3 stimulated cortisol secretion. In contrast, specific inhibition of the lipoxygenase system by nordihydroguaiaretic acid blocked IL-3 stimulated steroidogenesis while the effect of IL-6 was not affected. Neither IL-3 nor IL-6 altered cAMP levels significantly, whereas ACTH significantly induced cAMP levels in parallel to its steroidogenic effect. In conclusion, our data indicate that IL-3 and IL-6 stimulate the steroid secretion of bovine adrenocortical cells to a similar extent and with a similar time course. However, the effects of IL-3 and IL-6 are mediated through different, cAMP-independent pathways. While the stimulatory effect of IL-3 seems to be dependent on the lipoxygenase pathway, the effect of IL-6 on adrenocortical cortisol secretion is mediated through the cyclo-oxygenase pathway.
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PMID:Interleukin-3 and interleukin-6 stimulate bovine adrenal cortisol secretion through different pathways. 1069 40

CPH 82 is a non-steroid antirheumatic drug containing two benzylidenated podophyllotoxin glucosides with no affinity for the glucocorticoid receptor. Treatment with CPH 82 as single drug therapy significantly decreased serum and urinary cortisol and cortisol metabolites, serum adrenal androgens and urinary androgen metabolites, plasma ACTH and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and increased serum levels of sex hormone-binding globulin (SHBG). Significant positive correlations were found between serum TNF-alpha and plasma ACTH and between serum IL-6 and TNF-alpha on the one hand and serum and urinary cortisol and cortisol metabolites on the other. The initial action of CPH 82 on adrenal steroidogenesis may be a reduction in cytokine levels due to the drugs' antiinflammatory effect. This causes decreased ACTH stimulation, resulting in a reduced adrenocortical steroid secretion. Accumulation of the drug in the adrenal cortex may also affect adrenal steroidogenesis. The elevated SHBG levels may be caused by a weak estrogenic activity of the drug.
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PMID:Endocrine effects of the podophyllotoxine derivative drug CPH 82 (Reumacon) in patients with rheumatoid arthritis. 1077 20

Interleukins and their receptors are expressed intrinsically in the anterior pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lines. Here we examined the effects of IL-6 on propiomelanocortin (POMC) expression and ACTH production in corticotroph adenoma cells in vitro. We found that IL-6 stimulates both ACTH secretion and POMC gene expression in corticotroph adenoma cell cultures. This first demonstration of the stimulatory action of IL-6 on human corticotroph adenoma cell function provides further evidence for a direct action of IL-6 on corticotroph pituitary cells. We have confirmed previous reports of IL-6 production by corticotroph adenoma cells and in addition, demonstrated for the first time that the synthetic glucocorticoid dexamethasone is a potent suppressor of intratumoral IL-6 production. This intratumoral produced IL-6 may be in part responsible, in an autocrine manner, for the stimulation of ACTH synthesis and secretion. Our results suggest that IL-6 might play a role in the pathogenesis of Cushing's disease. However, elevated glucocorticoid levels in patients with Cushing's disease may prevent excessive action of IL-6 on ACTH production and tumor progression of corticotroph adenomas in vivo.
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PMID:Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas. 1092 17

Metabolic-endocrine dysfunctions, including hyperinsulinemia, hypertriglyceridemia, increased fat mass, and dysregulation of the hypothalamic-pituitary-adrenal axis, are common in myotonic dystrophy (MD). We hypothesized that increased production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may be important underlying mechanisms. We studied the diurnal rhythmicity of cytokines and cortisol, ACTH, and dehydroepiandrosterone in 18 men with adult onset MD and 18 controls. Morning levels of androstenedione, 17-hydroxyprogesterone, testosterone, and insulin were also determined. Genetic analyses were performed, including calculation of allele sizes. Median circulating 24-h levels of IL-6 (P < 0.001), TNF-alpha (P = 0.05), ACTH (P < 0.05), and cortisol (P < 0.05) were all significantly increased in MD, whereas dehydroepiandrosterone levels were decreased (P < 0.001). The diurnal rhythms of these cytokines/ hormones were disturbed in patients. Morning testosterone levels were decreased and insulin levels increased (P < 0.01 for both). Patients with high body fat mass had significantly increased insulin levels and decreased morning levels of cortisol, ACTH, and testosterone. IL-6 and TNF-alpha levels are increased and adrenocortical hormone regulation is disturbed in MD. Adiposity may contribute to these disturbances, which may be of importance for decreased adrenal androgen hormone production and metabolic, muscular, and neuropsychiatric dysfunction in MD.
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PMID:Abnormal cytokine and adrenocortical hormone regulation in myotonic dystrophy. 1099 4

Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) and their mRNAs are present in the human, rat, and bovine adrenal cortex. The release of these cytokines from adrenal cells is regulated by factors that alter adrenal function (e.g., ACTH, angiotensin II, interleukin-1). IL-6 and TNF type 1 receptors are also present on adrenocortical cells. Exposure to IL-6 increases cortisol or corticosterone release from human, bovine, and rat adrenal cells. IL-6 increases basal and ACTH-stimulated aldosterone release, but inhibits angiotensin II-stimulated aldosterone secretion from bovine adrenal cells. IL-6 increases dehydroepiandrosterone (DHEA) release from human cells, but decreases DHEA secretion from bovine cells. TNF alpha inhibits corticosterone release from normal rat adrenal cells or fragments, but increases corticosterone release from cholestatic rat adrenal slices. TNF alpha decreases cortisol release from bovine and fetal human adrenal cells, but increases cortisol release from adult human adrenal cells. TNF alpha inhibits aldosterone secretion from rat and bovine adrenocortical cells. TNF alpha does not affect DHEA secretion from fetal human adrenocortical cells, but inhibits basal and ACTH-stimulated DHEA release from bovine adrenal cell. Because IL-6 and TNF alpha are produced in the adrenal gland and modify adrenal steroid secretion, these cytokines may function as intraadrenal factors in the regulation of adrenal steroid secretion.
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PMID:Possible function of IL-6 and TNF as intraadrenal factors in the regulation of adrenal steroid secretion. 1126 91

Pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha), released from inflammatory foci, can activate the hypothalamus to produce corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP). These hypothalamic peptides in synergy increase ACTH production by the pituitary gland and hence corticosteroid (CS) secretion by the adrenal cortices. CS dampens inflammation. The pituitary also produces prolactin (PRL), which is pro-inflammatory, and macrophage inhibitory factor (MIF), which by counteracting the anti-inflammatory and immunosuppressive effects of CS, is pro-inflammatory. Lewis rats develop a variety of induced-autoimmune inflammatory conditions, such as streptococcal cell wall arthritis, whereas the histocompatible F344 Fisher rats are resistant to this condition. Lewis rats have a defective hypothalamic-pituitary adrenal (HPA) response to a variety of hypothalamic stimuli, but have augmented systemic secretion of AVP. Patients with rheumatoid arthritis (RA) have deficient CS with exaggerated PRL responses to inflammatory stimuli. Within inflammatory foci, CRH is pro-inflammatory. AVP, which augments autologous mixed lymphocyte reactions, can replace the IL-2 requirement for gamma IFN production by T cells via V1a receptors, and potentiates primary antibody responses, is also pro-inflammatory. Lewis rats have significantly high plasma levels, hypothalamic content, and in vitro release of AVP in comparison to the inflammatory disease-resistant Fischer rats. Immunoneutralization of AVP attenuates inflammatory responses. In Sprague-Dawley rats, AVP potentiates PRL secretion. Preliminary studies in patients with RA have shown that the circulating levels of AVP are significantly increased, which might be a compensatory response to low CS levels or a result of elevated levels of IL-6 in these patients but could nevertheless contribute to rheumatoid inflammation. A similar observation has been made in patients with ankylosing spondylitis.
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PMID:Perturbations of arginine vasopressin secretion during inflammatory stress. Pathophysiologic implications. 1126 12


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