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)

Previous studies have revealed that human breast fibroblasts secrete the cytokine, interleukin-6 (IL-6) which stimulates the ability of MCF-7 human breast carcinoma cells to convert estrone (E1) to the biologically more active 17 beta-estradiol (E2). This is mediated by an increase in reductive 17 beta-hydroxysteroid dehydrogenase (17-HSD) activity. In the studies described here, we have extended our observations using the anti-estrogen, tamoxifen, to demonstrate that in a steady state, endogenous intracellular concentrations of E2 have no effects on reductive 17-HSD activity (E1-->E2), but are already maximally inhibitory for the oxidative reaction (E2-->E1). Increasing intracellular concentrations of E2, however, stimulated the reductive 17-HSD in a dose-dependent manner. IL-6 stimulated the reductive pathway and was synergistic with E2. IL-6 is most likely acting through an E2-dependent mechanism, since tamoxifen completely reversed the effects of E2 and IL-6 separately and in combination. These observations suggest that tamoxifen may reduce intratissular levels of E2 by directly increasing oxidative 17-HSD activity and by blocking the actions of paracrine factors such as IL-6 which increase reductive 17-HSD activity.
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PMID:The anti-estrogen tamoxifen blocks the stimulatory effects of interleukin-6 on 17 beta-hydroxysteroid dehydrogenase activity in MCF-7 cells. 824 Sep 83

It has been demonstrated that reductive 17 beta-hydroxysteroid dehydrogenase activity (17-HSD) in the human breast cancer cell line MCF-7 can be stimulated by 17 beta-estradiol (E2), progesterone (P) and interleukin-6 (IL-6). We have examined the interactive effects of these factors on growth and reductive 17-HSD activity of MCF-7 cells cultured under defined conditions in phenol red-free medium. E2 stimulated growth of MCF-7 cells in a dose-dependent manner, while IL-6 had a growth inhibitory effect and in combination with E2, it reduced or abolished the stimulatory effects of the steroid. Both E2 and IL-6 stimulated 17-HSD activity by a maximum of 2- to 5-fold, but, in combination, the stimulatory effects ranged from 7- to 10-fold, indicating a strong synergism between the 2 factors. P had growth stimulatory effects on MCF-7, but when combined with IL-6 had no further positive or negative growth effects. Both factors stimulated reductive 17-HSD activity and simultaneous treatment with P and IL-6 indicated a synergy between the 2 factors. These results provide evidence of powerful interactive effects between steroidal and paracrine control of human breast epithelial cells in vitro.
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PMID:Interactive effects of interleukin-6, 17 beta-estradiol and progesterone on growth and 17 beta-hydroxysteroid dehydrogenase activity in human breast carcinoma cells. 839 37

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

Recent studies have questioned the benefits of early fluid resuscitation in hemorrhagic shock. The purpose of the current study is to evaluate the effects of early fluid resuscitation (HSE) (15 minutes), delayed fluid resuscitation (HSD) (60 minutes), and no fluid resuscitation (HSU) on cytokine levels, hepatic resting membrane potential (Em), renal function, and mortality. Eighty male Sprague-Dawley rats (350-450 g) were hemorrhaged 35% of their total blood volume and then received 40, 80, or 100 ml of crystalloid per kilogram as intravenous fluids (IVFs). The implementation of HSE resulted in stabilization of the Em (-29 mV), which was significantly different from that seen with HSD or HSU (-24 and -29 mV, respectively). The timing of resuscitation did not affect the elevation of tumor necrosis factor (TNFalpha) levels. The interleukin-6 (IL-6) levels for the HSE group were 81, 101, and 274 pg/ml for 40, 80, and 100 ml/kg, respectively. In contrast, HSD group IL-6 levels were 440, 566, and 632 pg/ml for 40, 80, and 100 ml/kg (p < 0.0001). IL-6 levels for the HSU group was 427 pg/ml, which was significantly different from that of the HSE group (p < 0.05). Urine output was present in 58% of the HSE rats but only 24% in the HSD rats and 0% of the HSU rats. Mortality was 11% for HSE, 58% for HSD, and 50% for HSU rats. Despite the recent studies questioning the benefits of early fluid resuscitation, these data show marked improvement in hepatic stability, the presence of urine output, decreased IL-6 levels, and significantly lower mortality when IVFs were given early after hemorrhagic shock. Furthermore, excessive fluid resuscitation (100 ml/kg) resulted in an increased inflammatory cytokine level and mortality and may account for the controversy.
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PMID:Improved survival with early fluid resuscitation following hemorrhagic shock. 1136 85