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)

Activation of the nitric oxide (NO) pathway over that of endothelin in the vessel wall, as judged from circulating endothelin and nitrate-nitrite (NN) levels, may partly account for the hypotension associated with vasodilation, diminished catecholamine sensitiveness and O2 extraction, and lactic acidemia in human septic shock. In a prospective study, 14 consecutive patients with septic shock and a pulmonary artery catheter in place were included. For 3 days after admission, serial measurements of hemodynamic variables and plasma levels of endothelin and NN were done. The patients had a hyperdynamic circulation. Except for a higher final blood lactate level and more treatment with vasoconstricting catecholamines in nonsurvivors, global hemodynamic and O2-related variables did not differ between outcome groups. On the day of admission, circulating endothelin and NN levels were elevated and related to elevated levels of tumor necrosis factor-alpha and interleukin-6. The levels of endothelin increased in time in nonsurvivors as compared with survivors. The NN levels declined in survivors but not in nonsurvivors. The systemic vascular resistance indices (SVRI), global O2 extraction ratios, and blood lactate levels directly related to the endothelin levels. SVRI and global O2 extraction ratios inversely, and the lactate blood levels directly, related to NN levels, and the hemodynamic and metabolic parameters related directly to the ratio between endothelin and NN plasma levels on the days of the study. The vessel wall factors did not relate to the creatinine levels. The results suggest that the hemodynamic and metabolic peripheral abnormalities of human septic shock are mediated in part by cytokine-activated endothelin and NO systems in the vessel wall. They also suggest that increased production rather than diminished renal clearance accounts for elevated levels of NN and endothelin and that the latter are associated with a poor outcome.
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PMID:Circulating endothelin and nitrate-nitrite relate to hemodynamic and metabolic variables in human septic shock. 1018 67

The objective of this study was to determine whether the measurements of amniotic fluid nitric oxide metabolite (NOx: nitrate + nitrite) concentrations could be a clinically useful marker to differentiate between intra-amniotic mycoplasma and nonmycoplasma infections. Amniocentesis was performed on 76 pregnant women with suspicion of intra-amniotic infection. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture with either mycoplasma or nonmycoplasma infections. Rapid amniotic fluid tests for Gram stain, glucose, leukocyte counts, interleukin-6, and NOx were performed. Amniotic fluid NOx was measured with aspergillus nitrate reductase and Griess reagent. Interleukin-6 was determined by enzyme immunoassays. Amniotic fluid NOx and interleukin-6 were normalized by amniotic fluid creatinine levels. Patients with intra-amniotic mycoplasma (n = 7) and nonmycoplasma infections (n = 8) had significantly higher amniotic fluid leukocyte counts and interleukin-6 concentrations and significantly lower amniotic fluid glucose levels than noninfected controls (n = 61). Amniotic fluid concentrations of NOx were significantly higher in those with intraamniotic nonmycoplasma infection as compared to those with intraamniotic mycoplasma infection and noninfected controls (NOx: 3.35+/-0.74 vs. 2.03+/-0.41 micromol/mg creatinine, p = 0.005, and 3.35+/-0.74 vs. 1.72+/-0.07 micromol/mg creatinine, p < 0.0001, respectively). However, patients with intra-amniotic mycoplasma infection did not differ significantly from noninfected controls. Our data indicate that clinical characteristics of intra-amniotic mycoplasma infection may differ from intra-amniotic nonmycoplasma infection. As delivery is not always indicated in intra-amniotic mycoplasma infection, elevated rapid amniotic fluid tests (leukocyte counts, interleukin-6, and glucose) may not be appropriate in the clinical management of intra-amniotic mycoplasma infection. In addition to these rapid amniotic fluid tests, incorporation of the measurement of amniotic fluid NOx may be of clinical importance in the differentiation and management of patients with suspected intra-amniotic mycoplasma and nonmycoplasma infection.
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PMID:Nitric oxide: a clinically important amniotic fluid marker to distinguish between intra-amniotic mycoplasma and non-mycoplasma infections. 1045 27

The effect of four macrolide antibiotics (roxithromycin, clarithromycin, erythromycin, and azithromycin) on the generation of some mediators and cytokines involved in the inflammatory process has been studied both in vivo and in vitro. Rat carrageenin pleurisy was used as a model of acute inflammation, and the macrolides were administered (10, 20, and 40 mg/kg p.o.) 1 h before the carrageenin challenge. Exudate volume and leukocyte accumulation were both dose-dependently reduced by roxithromycin, clarithromycin and erythromycin in either normal or adrenalectomized animals. Furthermore, in normal rats, prostaglandin (PG)E(2), nitrate plus nitrite, and tumor necrosis factor-alpha levels in pleural exudate were significantly reduced by these macrolides. Roxithromycin appeared more effective than erythromycin and clarithromycin, whereas azithromycin only slightly affected the inflammatory reaction. None of the macrolides were able to modify leukotriene B(4) exudate levels. In vitro experiments have shown that the four macrolides (5-80 microM) reduced in a concentration-dependent manner the production of 6-keto-PGF(1alpha), NO(2)(-), tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by lipopolysaccharide-stimulated J774 macrophages. In J774 cells, the inhibition of 6-keto-PGF(1alpha) and NO(2)(-) production by roxithromycin and erythromycin was not dependent on direct inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activity because it appears to be related to the inhibition of cyclooxygenase-2 and inducible nitric oxide synthase protein expression. In conclusion, the present study shows that macrolide antibiotics have anti-inflammatory activity, which likely depends on their ability to prevent the production of proinflammatory mediators and cytokines, and suggest that these agents, particularly roxithromycin, can exert therapeutic effects independently of their antibacterial activity.
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PMID:Anti-inflammatory activity of macrolide antibiotics. 1060 43

The physiopathological events following thermal injury are not limited to the surface effects of heat but are also related to acute inflammatory reactions. Both tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are important mediators of the acute and severe inflammatory reaction in thermal injury. Surgical manipulation of the burn wound is known to prevent excessive release of cytokines. Cerium nitrate--a rare earth element--has been reported to have a protective effect against postburn immunosuppression. The aim of this study was to compare the effects of burn wound debridement and treatment with cerium nitrate bathing on the serum levels of TNF-alpha and IL-6 in rats. Treatment by cerium nitrate bathing prevented the elevation of TNF-alpha levels in the early period after thermal injury. The experimental study showed, as in other studies, that high levels of IL-6 appear to inhibit TNF-alpha elevation. High levels of IL-6 and, as a result, relatively low levels of TNF-alpha in the early period of thermal injury may limit the severity of the inflammatory reaction, which is caused by TNF, the most potent inflammatory cytokine. Since similar levels of IL-6 and TNF-alpha were achieved by both cerium nitrate bathing and burn wound debridement, cerium nitrate may be considered as equivalent to prompt excision of burn eschar.
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PMID:Effects of cerium nitrate bathing and prompt burn wound excision on IL-6 and TNF-alpha levels in burned rats. 1063 Mar 18

Most in vivo studies demonstrating decreased activities of hepatic cytochromes P450 with inflammation have used Gram-negative bacterial lipopolysaccharide (LPS) as the inflammatory stimulant. But products of Gram-positive bacteria, such as staphylococcal enterotoxin B (SEB), also stimulate inflammatory mediators, albeit with a different pattern than LPS. Therefore, effects of SEB on the regulation of murine constitutive P450s were determined in this study and compared with those of LPS. LPS-responsive C3H/HeN and LPS-unresponsive C3H/HeJ mice were injected with either LPS (0.5 mg/kg) or SEB (0.66 to 6.6 mg/kg), and hepatic cytochromes P450 and serum tumor necrosis factor-alpha, interleukin-6, nitrate/nitrite, and serum amyloid A concentrations were determined up to 24 hr. HeJ mice were generally less responsive than HeN mice to both stimuli, with lower cytokine, nitrate/nitrite, and serum amyloid A responses. However, in both mouse strains SEB caused more prolonged cytokine, higher nitrate/nitrite, and lower serum amyloid A concentrations than LPS. Despite these differences, in HeN mice, after both SEB and LPS administration, total P450 concentrations were equally depressed by 40%. Both SEB and LPS depressed CYP1A1 and 1A2 microsomal protein concentrations by 45 and 30%, respectively; CYP2E1 by 64%; and CYP3A by 70%. There was comparable inhibition of enzymatic activities. In HeJ mice, SEB was only slightly more effective in depressing P450s than LPS, as might be expected. These data showed that the Gram-positive bacterial inflammatory stimulant SEB caused effects on murine hepatic cytochromes P450 similar to those of LPS, even though the pattern of inflammatory mediators induced after SEB exposure was different.
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PMID:Depression of constitutive murine cytochromes P450 by staphylococcal enterotoxin B. 1073 30

The etiology and treatment of a solitary bone cyst have remained undefined. Surgical treatments have not been encouraging, because a less invasive corticosteroid-injection treatment has afforded good results. However, there has been little scientific rationale supporting corticosteroid treatment. In recent reports, bone-resorbing factors, including matrix metalloproteinases, prostaglandins, interleukin-1, and oxygen free radicals, have been demonstrated in the cyst fluid. To better elucidate the pathophysiology of the solitary bone cyst, we examined the activities of nitric oxide and cytokines in the cyst fluid as well as in the cyst membrane. The levels of nitrate and nitrite were significantly higher in the cyst fluid than in serum. Immunostaining of cells in the stroma and lining cells of the cyst wall was strongly positive for inducible nitric synthase. The levels of interleukin-6 and interleukin-1beta in the cyst fluid were elevated, and cells in the cyst membrane were positive for tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta. Cultured cells from the cyst membrane were induced in the production of nitrate and nitrite in response to cytokine treatment. These findings suggest that the solitary bone cyst was in a state favorable for the production of nitric oxide.
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PMID:Increased concentrations of nitrate and nitrite in the cyst fluid suggesting increased nitric oxide synthesis in solitary bone cysts. 1081 30

Immunosuppression may have an important impact on early graft coronary endothelial injury. We investigated functional and morphologic coronary alterations, myocardial expression, and cardiac release of possible mediators of allograft vasculopathy within 6 months after cardiac transplantation with respect to different immunosuppressive regimens. Epicardial and microvascular endothelium-dependent and endothelium-independent vasomotor function and epicardial intimal thickening were measured in 8 transplant recipients treated with cyclosporin A (CyA), azathioprine, and prednisone (group 1), 9 transplant recipients treated with tacrolimus (TKL), azathioprine, and prednisone (group 2), and 14 patients treated with TKL, mycophenolate mofetil (MMF), and prednisone (group 3). The gene expressions of inducible and endothelial nitric oxide synthase (iNOS and eNOS), endothelin-1, prostacyclinsynthase, and thromboxansynthase were analyzed in endomyocardial biopsy specimens using semiquantitative reverse transcription polymerase chain reaction. Transcardiac cytokine release, endothelin-1, and nitrate-release were determined from plasma samples. Epicardial endothelial dysfunction (vasoconstriction to acetylcholine > 10%) and microvascular smooth muscle cell dysfunction (flow velocity increase to adenosine and nifedipine < 2.0) were enhanced in heart transplant recipients immunosuppressed with TKL, azathioprine, and prednisone. The prevalence of epicardial dysfunction was 78% in group 2 versus 44% and 46% in group 1 and 3 (p < 0.05), respectively. The prevalence of microvascular dysfunction was 56% in group 2 versus 13% and 7% in group 1 and 3 (p < 0.02), respectively. Coronary vasomotor dysfunction was associated with increased myocardial iNOS expression (p < 0.05), decreased eNOS expression (p < 0.05), and enhanced cardiac immunoreactive interleukin-6 (p < 0.01). Coronary intimal thickening was not different between the groups. The combination of TKL and MMF appears to be superior to TKL and azathioprine (and comparable to CyA and azathioprine) concerning preservation of early coronary vasomotor function, eNOS expression, iNOS suppression as well as cardiac interleukin-6 release. This may have an important impact on subsequent development of transplant coronary atherosclerosis.
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PMID:Coronary vasomotor dysfunction in the cardiac allograft: impact of different immunosuppressive regimens. 1111 79

1. M40403 is a low molecular weight, synthetic manganese containing superoxide dismutase mimetic (SODm) that removes superoxide anions (*O2-) without interfering with other reactive species known to be involved in inflammatory responses (e.g. nitric oxide, NO and peroxynitrite, ONOO-). 2. As such, M40403 represents an important pharmacological tool to dissect the roles of *O2- in acute and chronic inflammation. For this purpose, the pharmacological profile of M40403 was evaluated in carrageenan-induced pleurisy. 3. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of neutrophils (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), prostaglandin E2 (PGE2), tumour necrosis factor alpha, (TNFalpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and interleukin-10 (IL-10). 4. All parameters of inflammation were attenuated by M40403 except for NOx, PGE2 and IL-10 which remained unaltered. Furthermore, carrageenan induced an upregulation of the adhesion molecules ICAM-1 and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) as determined by immunohistochemical analysis of lung tissues. 5. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine and PARS was reduced by M40403. 6. These results clearly indicate that *O2- plays a critical role in the development of the inflammatory response by altering key components of the inflammatory cascade. Therefore, synthetic enzymes of SOD such as M40403, offers a novel therapeutic approach for the management of various inflammatory diseases where these radicals have been postulated to play a role.
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PMID:Pharmacological manipulation of the inflammatory cascade by the superoxide dismutase mimetic, M40403. 1118 22

Interleukin-6 (IL-6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 patients with MS and 23 control subjects. Mean CSF IL-6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL-6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL-6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL-6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.
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PMID:Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients. 1209 27

The aim of this study was to examine solvent-associated effects on blood cytokine levels, antioxidant enzyme activities, and malondialdehyde (MDA) concentration in house painters. Trace element (Cu and Zn) and nitrite and nitrate levels as well as protein concentrations in erythrocytes and serum were determined. Thirty male house painters and 30 male clerical workers were included in the study. There were 13 smokers and 17 nonsmokers in each group. Hemoglobin concentrations were significantly lower in house-painter blood compared to controls. House painters had significantly higher concentrations of erythrocyte protein (excluding hemoglobin), whereas no significant difference was observed between serum protein levels. Proinflammatory cytokine levels, such as tumor necrosis factor-alpha and interleukin-8, were significantly increased in house painters' sera. Interleukin-6 was below the detection limit of the assay in both groups. Interleukin-1beta and cytokine receptor interleukin 2R concentrations were not significantly affected. Furthermore, a three- to fourfold increase in nitrite and nitrate concentrations was found in house painters' sera. Serum superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities were significantly lower in house painters compared to controls. Malondialdehyde (MDA) concentration, a measure of lipid peroxidation, was found to be significantly elevated. In house painters, erythrocyte carbonic anhydrase and catalase activities were elevated approximately 11- fold and 2-fold, respectively. Zinc levels were significantly decreased in house painters' sera. Smoking was not found to be a major confounder for the association between solvent exposure and blood parameters.
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PMID:Effects of long-term solvent exposure on blood cytokine levels and antioxidant enzyme activities in house painters. 1216 7


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