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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reprocessing of dialyzers is often performed with nonsterile solutions possibly contaminated with bacterial-derived cytokine-inducing substances. We investigated the retention of cytokine-inducing substances inside the dialyzer during reprocessing in a closed loop in vitro hemodialysis system using a polyamide high flux membrane. After the first in vitro circulation of human whole blood, rinse of the blood compartment (BC) and reverse ultrafiltration (RUF) was performed with either cytokine-inducing substance-free saline or saline contaminated with filtrates from Pseudomonas cultures (6 ng/ml LAL-reactive material); subsequently, dialyzers were stored in 2% formaldehyde. Dialyzers were rinsed with approximately 15 liters pyrogen-free saline before the second circulation using blood from the same donor; the effluates were free of cytokine-inducing substances and formaldehyde. Before and after the blood circulations, peripheral blood mononuclear cells (PBMC) were separated and total production of IL-1 alpha and IL-1 beta was determined after overnight incubation. In noncirculated PBMC as well as in PBMC separated after whole blood circulation with pyrogen-free processed dialyzers, production of IL-1 beta was not detectable. After contaminated rinse of the BC, production of IL-1 beta could be observed (1,600 +/- 1,100 pg/ml, mean +/- SEM). When pyrogen-free RUF was performed after contaminated BC rinse, IL-1 beta production averaged 163 +/- 92 pg/ml when using reused dialyzers, but 1,820 +/- 880 pg/ml when using new dialyzers. After reuse with pyrogen-free BC-rinse and contaminated RUF no IL-1 beta synthesis was observed; however, when pyrogen-free BC-rinse and contaminated RUF was applied to new dialyzers, IL-1 beta synthesis averaged 1,620 +/- 1,200 pg/ml. We conclude that cytokine-inducing substances are retained inside the dialyzer, probably by adsorption to the membrane as well as to the protein layer covering the membrane and are still biologically active after sterilisation. Cytokine-inducing substances adsorbed to the protein layer can be partially removed by RUF. Finally, the protein layer on the membrane appears to reduce the convective transfer of cytokine-inducing substances from the dialysate into the blood compartment.
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PMID:Retention of cytokine-inducing substances inside high-flux dialyzers. 871 62

The ovulatory process resembles an inflammatory reaction with an infiltration of leukocytes, production of inflammatory mediators such as cytokines, and a general edema and hyperemia. Nitric oxide (NO), a potent vasodilator and the main mediator of macrophage tumoricidal and bacteriocidal activities, is known to participate in inflammatory reactions and has been shown to mediate the interleukin-1 beta (IL-1 beta)-directed tissue-remodeling events within the ovary. The regulation by NO of ovulation rate, leukocyte distribution, and steroid release in the rat ovary was investigated through use of a combination of in vivo and in vitro models of ovulation and a competitive inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), of the NO synthase (NOS) enzyme. Subcutaneous L-NAME (1.5 x 10(-4) mol/kg) administration significantly reduced the in vivo ovulation rate of eCG/hCG-primed rats (L-NAME-treated: 10.6 +/- 1.8 [mean +/- SEM] oocytes per ovary [O/O], 11.0 +/- 1.2 rupture sites per ovary [RS/O]; saline-treated: 18.0 +/- 1.8 O/O, 19.4 +/- 1.1 RS/O; p < 0.01) at 20 h post-hCG. These results were reflected in vitro, where addition of L-NAME (3.5 x 10(-5) mol/L) to LH (0.1 microgram/ml)-perfused ovaries decreased ovulation rate from 8.2 +/- 1.6 to 2.7 +/- 1 ovulations per ovary (p < 0.05) and simultaneously decreased nitrite accumulation at the completion of perfusions from 16.5 +/- 1.9 to 4.1 +/- 0.5 nmol/ml (p < 0.001). The addition of L-NAME to LH+IL-1 beta (4 ng/ml)-perfused ovaries decreased ovulation rate from 15.2 +/- 2.4 to 0.8 +/- 0.8 ovulations per ovary (p < 0.001) and simultaneously decreased nitrite accumulation at 22 h from 22.8 +/- 2.2 to 1.9 +/- 0.6 nmol/ml (p < 0.001). Studies analyzing and manipulating perfusion flow rate indicated that the L-NAME effects on ovulation rate are primarily due to a reduction in flow rate resulting from inhibition of NO, which may be a consequence of the known vasoconstrictor effects of NOS inhibitors. The observed reduction of in vivo ovulation rate by NO inhibition at 20 h post-hCG was associated with a significant reduction in thecal MCA149+ neutrophils at 12 h post-hCG, the expected time of ovulation (L-NAME-treated: 98.4 +/- 9.2 cells per thecal area; saline-treated: 211.5 +/- 11.5 cells per thecal area; p < 0.001), while ED1+ monocytes/macrophages underwent similar but nonsignificant changes. Plasma (20 h post-hCG) and perfusate progesterone were not different with L-NAME treatment, while perfusate estradiol levels were markedly reduced upon addition of L-NAME, suggesting a role for NO in ovulation but not in the process of luteinization. In summary, deprivation of NO by use of the competitive inhibitor, L-NAME, led to fewer ovulations, reduced accumulation of nitrite, a decreased neutrophil count in the theca of preovulatory follicles, and reduced estradiol secretion, while progesterone release remained unaffected. The NO pathway may therefore play an important role in the regulation of ovulation and the mediation of IL-1 beta's pro-ovulatory effects. There are likely to be primarily vascular effects, but also a nonvascular component, to the NO regulation of ovulation, with both components indirectly affecting ovulatory leukocyte distribution and steroid secretion.
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PMID:Inhibition of nitric oxide: effects on interleukin-1 beta-enhanced ovulation rate, steroid hormones, and ovarian leukocyte distribution at ovulation in the rat. 878 97

Some studies suggest that estrogen acts on bone by decreasing the production of interleukin-6 (IL-6), a cytokine that increases bone resorption, by osteoblasts or bone marrow cells. However, other studies have not confirmed this, possibly because of a low and variable number of estrogen receptors (ER) in the model systems used. Thus, we employed a recently developed human fetal osteoblast cell line with high levels of ER. Treatment (n = 4 experiments) with 0.01 to 10 nM of 17 beta-estradiol had no effect on the constitutive production of IL-6. However, stimulated production, induced by treatment with IL-1 beta plus tumor necrosis factor-alpha (TNF-alpha), was reduced in a dose-dependent manner to 74 +/- 3% (mean +/- SEM) of control (p < 0.01). This response was blocked by cotreatment with the type II antiestrogen ICI 182,780. Treatment with hydrocortisone (1 microM), a known inhibitor of IL-6 production in many cell types, reduced IL-6 production to 17 +/- 1% of control (p < 0.001). As assessed by Northern analysis, treatment (n = 3 experiments) with 0.01-10 nM of 17 beta-estradiol decreased steady-state levels of IL-6 mRNA in a dose-dependent manner. These data support the hypothesis that at least part of the antiresorptive action of estrogen in humans is mediated by decreased production of IL-6 by osteoblastic cells.
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PMID:Estrogen inhibits interleukin-6 production and gene expression in a human osteoblastic cell line with high levels of estrogen receptors. 882 43

5-Hydroxyeicosatetraenoic acid (5-HETE) is an arachidonic acid (AA) metabolite derived from the lipoxygenase pathway which is capable of inducing uterine contractions. The purpose of this study was to determine a). whether 5-HETE concentrations in amniotic fluid increase before or after the onset of labor and b). whether acetylsalicylic acid (ASA) could modulate the production of 5-HETE by human amnion cells. 5-HETE concentrations are increased in amniotic fluid before the onset of labor. Furthermore, ASA treatment as expected inhibited PGE2, but also significantly increased 5-HETE production by amnion cells. 5-HETE concentrations on average increased by greater than 2.5 fold (p < 0.001) in amniotic fluid prior to spontaneous labor when compared with samples obtained from the same patients earlier in gestation and therefore may be important in mechanisms regulating the onset of labor. ASA provokes an increase in 5-HETE biosynthesis by amnion cells: control media 2.60 +/- 1.5, ASA treatment alone 5.17 +/- 0.20, IL-1 beta alone 6.39 +/- 2.1, and ASA + IL-1 beta 8.95 +/- 1.2 (mean +/- SEM) picograms per microgram protein per 16 hours. These findings may explain in part why cyclooxygenase inhibitors are not always successful in treating women with preterm labor.
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PMID:5-Hydroxyeicosatetraenoic acid and human parturition. 887 35

Bronchial epithelium plays a major role in the regulation of inflammatory reactions in the airways. It is thought to be a possible target for glucocorticoid therapy. Glucocorticoid responsiveness requires the presence of specific glucocorticoid receptors (GR). Until now, little was known about the presence of such receptors in the human bronchial epithelium. In this study we demonstrated the expression of GR messenger ribonucleic acid (mRNA) in two simian virus (SV)-40/adenovirus-transformed human bronchial epithelial cell lines, BEAS S6 and BEAS 2B. In a whole cell dexamethasone binding assay, BEAS S6 and BEAS 2B cells were found to possess (mean +/- SEM) 28.9 +/- 4.4 x 10(3) and 32.1 +/- 5.7 x 10(3) binding sites per cell, respectively, with dissociation constant (Kd) values of 8.2 +/- 1.5 and 8.6 +/- 2.4 nM, respectively. Using electrophoretic mobility shift assays we demonstrated the binding of nuclear translocated GR to specific sites on deoxyribonucleic acid (DNA), named glucocorticoid responsive elements (GRE). Lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta) significantly increased the number of GR per cell (median = 312% and 171% of control, respectively; p < 0.05), but significantly reduced the ligand affinity of these receptors, i.e. increased the Kd (median = 410% and 145% of control, respectively; p < 0.05) in BEAS 2B cells. These results indicate that the bronchial epithelium may be an actual target for glucocorticoid therapy. Inflammatory mediators, such as IL-1 beta and LPS, modulate the number and ligand affinity of these GR. Therefore, the response of bronchial epithelium to glucocorticoid therapy may be modulated by airway diseases associated with inflammation.
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PMID:Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1 beta, TNF-alpha and LPS. 890 64

During adult cardiac surgery the plasma pro-inflammatory cytokine response is balanced by a phased anti-inflammatory cytokine response. Whether a similar balanced plasma pro- and anti-inflammatory cytokine response occurred in paediatric cardiac surgery was investigated. Changes in intra-pulmonary cytokine balance by measuring bronchoalveolar lavage (BAL) cytokine content were also estimated. Plasma and BAL samples were obtained from 10 children (aged 15 months to 10 years) 10 min after induction of anaesthesia (sample 0), 5 min after the onset of cardiopulmonary bypass (CPB) (sample 1), 10 min after release of the aortic cross clamp (sample 2), and 2 and 24 h after the end of CPB (samples 3 and 4). BAL and plasma was assayed for interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), IL-8, IL-10, interleukin 1 receptor antagonist (IL-1ra) and the TNF soluble receptors (TNFsrs). There was a phased plasma anti-inflammatory response commencing with IL-10 (sample 2), and followed by significant increases in IL-1ra (samples 3, 4 and 5) and TNF soluble receptors (sample 5). Plasma TNF-alpha and IL-1 beta concentrations were not significantly elevated from baseline. Mean baseline plasma IL-8 was 30 (SEM 9) pg/ml. This was significantly elevated at sample 4 (112 (SEM 68) pg/ml). In BAL, only IL-8 and IL-10 were significantly elevated after CPB as compared with baseline. During paediatric cardiac surgery there is a significant increase in plasma and BAL IL-8. This is balanced within the plasma by a phased anti-inflammatory cytokine response, and within the lung by IL-10.
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PMID:The balance of pro and anti-inflammatory cytokines in plasma and bronchoalveolar lavage (BAL) at paediatric cardiac surgery. 893 84

Gaucher's disease is characterized by hepatosplenomegaly, bone-marrow infiltration, osteonecrosis and bone thinning, associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. To investigate the possible role of cytokines in the systemic and local manifestations of established Gaucher's disease, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) were measured in freshly-separated serum. Samples from eight male and 14 female patients with type 1 Gaucher's disease were compared with sera from 22 healthy age- and sex-matched controls. Concentrations of IL-6 and IL-10 were significantly elevated in sera from patients with Gaucher's disease (11.9 +/- 1.8 (SEM) pg/ml and 5.4 +/- 0.5 (SEM) pg/ml, respectively) compared with those of controls (4.1 +/- 0.9 (SEM) and 0.8 +/- 0.3 (SEM) pg/ml, p < 0.0001). No significant differences in concentrations of TNF alpha or IL-1 beta were identified. IL-6 has been implicated in the development of localized osteolysis in multiple myeloma and in the development of post-menopausal osteoporosis. High concentrations of IL-6 in the serum of patients with Gaucher's disease may thus reflect the development of the bone lesions commonly associated with this disorder. Since IL-6 and IL-10 are important regulators of lymphocyte growth and differentiation, and IL-6 concentrations were significantly raised in patients with oligo- or polyclonal increases in serum immunoglobulins, enhanced release of these cytokines from pathological macrophages provides a pathological link between Gaucher's disease and associated lympho-proliferative disorders.
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PMID:Pro-inflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-10. 909 85

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 +/- 3 years (mean +/- SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1 beta and IL-6 were found to be 15-fold higher on admission (122 +/- 9 pg mL-1 and 60 +/- 4 pg mL-1 respectively), whereas TNF-alpha was three-fold higher (102 +/- 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 +/- 1 mg L-1), whereas fibronectin levels were reduced (242 +/- 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-alpha serum level (127 +/- 7 vs. 86 +/- 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-alpha (-7.2 +/- 0.7 vs. -3.8 +/- 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 +/- 3.0 vs. -54.6 +/- 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 +/- 1.0 vs. 11.7 +/- 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.
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PMID:Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia. 913 79

The impact of continuous hemofiltration (CHF) using a polyacrylonitrile membrane on the kinetics of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and their inhibitors (soluble TNF receptors [sTNFrI, sTNFrII], interleukin-1 receptor antagonist [IL-1Ra]) was assessed in nine oliguric patients suffering from systemic inflammatory response syndrome. Blood and plasma flow (Qb, Qp), sieving coefficient (SC), plasma and ultrafiltrate clearances (Kp, Kuf), and plasma extraction rates (ERp) were calculated at different time points using standard formulas. No significant improvement of hemodynamics or gas exchange was noted following HF but a significant increase in serum bicarbonate occurred after 24 h (P < 0.05). TNF alpha was detected in plasma from all patients (153 +/- 2.3 pg/mL [mean +/- SEM]). None of the patients had detectable IL-1 beta levels. High levels of the TNF receptors (sTNFrI 20.338 +/- 2.431 pg/mL; sTNFrII 17.839 +/- 2.630 pg/mL) and IL-1Ra (19.775 +/- 3.943 pg/mL) were found in all patients. Upon initiation of hemofiltration (HF), the mean individual sTNFrI/TNF alpha ratio amounted to 269 +/- 84.6 and the sTNFrII/TNF alpha ratio to 249 +/- 91.8. Mean ultrafiltrate volume (Vuf) was 11.8 +/- 0.4 L/day. Appreciable sieving of IL-1Ra (SC 0.45 +/- 0.10), but not of the other cytokines, was noted (SC TNF alpha, sTNFrI, sTNFrII < 0.09). Despite minimal Kuf of TNF alpha, sTNFrI, and STNFrII (Kuf < 0.8 mL/min), appreciable Kp was noted, suggesting that membrane adsorption occurs (Kp approximately 8 mL/min). There was a nonsignificant increase of the ratios between both TNF receptors and TNF alpha across the filter (sTNFrI/TNF alpha ratio [pre] 231 +/- 37.9 versus [post] 312 +/- 75.3); sTNFrII/TNF alpha ratio [pre] 211 +/- 42.1 versus [post] 291 +/- 79.3). Appreciable Kp of IL-1Ra was noted (Kp 17.3 +/- 1.61 mL/min), which was only in part due to Kuf (4.0 +/- 0.86 mL/min). There was a significant decrease of IL-1Ra levels across the membrane, both overall ([pre] 20.223 +/- 2.282 versus [post] 16.637 +/- 2.039 pg/mL; P < 0.01) and at different time points (P < 0.01). Only for IL-1Ra was significant extraction from plasma noted (ERp 26 +/- 6.0%). Plasma levels of TNF alpha, sTNFrI, sTNFrII, and IL-1Ra were not altered by 24 h of CHF. In conclusion, both cytokines and cytokine inhibitors can be removed from the circulation, either by convective transport or by membrane adsorption. Using low-volume HF (Vuf approximately 12 L/day), no impact on cytokine plasma levels nor the patients hemodynamics or gas exchange was noted. The appreciable SC of IL-1Ra (0.45), however, suggests that HF with high(er) UF volumes (> 50 L/day) may be able to achieve reductions in plasma levels of some peptide (anti)mediators. However, whether this aspecific elimination of both mediators and antimediators may alter the clinical course in critically ill patients remains to be investigated.
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PMID:Impact of continuous hemofiltration on cytokines and cytokine inhibitors in oliguric patients suffering from systemic inflammatory response syndrome. 915 61

During systemic infection, the serum lipopolysaccharide binding protein (LBP) binds to the lipid A component of bacterial endotoxins and facilitates its delivery to the CD 14 receptor on the cell surface of macrophages, where proinflammatory cytokines are released. There is no knowledge to date whether LBP is also present in the effluent of patients with continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis. We investigated the dialysis effluent of 37 patients with CAPD peritonitis for immunoreactive LBP, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta and compared the findings with the cytokine levels in 20 noninfected CAPD patients. The mean +/- SEM concentrations of LBP, TNF-alpha, and IL-1 beta were significantly higher in the effluent of patients with peritonitis than in noninfected CAPD effluent. In comparison to controls (0.23 +/- 0.05 microgram/mL), LBP was 0.68 +/- 0.13 microgram/mL in the effluent of patients with CAPD-associated infectious peritonitis. For TNF-alpha, levels were 0.50 +/- 0.25 pg/mL in the control effluent versus 124.7 +/- 46.6 pg/mL in the effluent of peritonitis patients. For IL-1 beta the levels were 0.24 +/- 0.14 pg/mL in the control effluent and 71.23 +/- 17.53 pg/mL in the peritonitis patients. Our findings demonstrate that LBP is significantly elevated in the effluent of CAPD patients during an episode of CAPD-associated peritonitis and might be used as a marker of intraperitoneal bacterial infection.
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PMID:Lipopolysaccharide binding protein: a marker for intraperitoneal bacterial infection in patients with CAPD peritonitis. 936 Jun 83


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