Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our recent studies suggest that lipocortin 1 (LC1), a potential mediator of the anti-inflammatory, antiproliferative and anti-fever actions of glucocorticoids in peripheral tissues, may also contribute to the powerful negative feedback actions of the steroids on the hypothalamo-pituitary-adrenal (HPA) axis. In the present study we have used (1) an in vitro model to examine the influence of a specific neutralizing monoclonal anti-LC1 antibody (anti-LC1 mAb) on the capacity of dexamethasone to suppress the cytokine-induced release of the 41-amino acid corticotropin-releasing factor (CRF-41) and arginine vasopressin (AVP) from the rat hypothalamus and (2) a passive immunization protocol to assess the contribution of LC1 to the inhibitory actions of dexamethasone on the HPA responses to immunological (i.p. injection of interleukin 1 beta, IL-1 beta) and surgical (laparotomy under ether anaesthesia) stress. In vitro, Il-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml), IL-6 (10 ng/ml) and IL-8 (1 ng/ml) each caused significant increases in the release of immunoreactive (ir)-CRF-41 and ir-AVP from hypothalami removed from rats adrenalectomized 10-12 days before autopsy; these responses were readily inhibited by preincubation of the tissue with dexamethasone (10(-7) M). The inhibitory actions of the steroid were attenuated and, in many instances, abolished by inclusion in the medium of a monoclonal anti-LC1 antibody (LC1 mAb, diluted 1:15,000); an isotype-matched control antibody (antispectrin alpha+beta, diluted 1:15,000) was ineffective in this regard. IL-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml) and IL-6 (10 ng/ml) also initiated similar increases in the release of CRF-41 and AVP from hypothalami from intact rats which were effectively blocked by dexamethasone (10(-7) M). However, although the inhibitory actions of the steroid on the pharmacologically evoked release of CRF-41 were specifically overcome by anti-LC1 mAb (diluted 1:15,000), the steroid blockade of AVP release was not. In vivo, rats pretreated with either a polyclonal anti-LC1 antibody (anti-LC1 pAb, 1 ml/day s.c. for 2 days) or a corresponding volume of a nonimmune sheep serum (NSS) responded to immunological (IL-1 beta, 3 micrograms/kg i.p.) or surgical (laparotomy under ether anaesthesia) trauma with significant increases in the serum ACTH and corticosterone concentrations. In the NSS-treated groups, dexamethasone (100 micrograms/kg), which had no effect on the prestress concentrations of ACTH and corticosterone in the blood, completely prevented the HPA responses to both IL-1 beta and laparotomy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunoneutralization of lipocortin 1 reverses the acute inhibitory effects of dexamethasone on the hypothalamo-pituitary-adrenocortical responses to cytokines in the rat in vitro and in vivo. 756 34

Interleukin-8 (IL-8) has been shown to be a chemotactic factor for neutrophils, T-lymphocytes and eosinophils, but it is unknown whether the IL-8-induced inflammatory cell accumulation into the airways can cause the bronchial hyperresponsiveness (BHR) characteristic of asthma. IL-8 at a dose of 0.5 or 5 micrograms/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilated through tracheal cannula and lateral pressure at the cannula (Pao) was measured as an overall index of airway responses to increasing concentrations of inhaled histamine (25, 50, 100, and 200 micrograms/ml). The IL-8 treatment significantly enhanced bronchial responsiveness to histamine in a dose-dependent manner (ANOVA P < 0.01). The provocative concentration of histamine causing a 100% increase in Pao (PC100) at a dose of 0.5 and 5 micrograms/kg of IL-8 was 68.1 (GSEM 1.12) and 35.6 (GSEM 1.25) micrograms/ml, respectively. The latter was significantly (P < 0.01) lower than that in control animals treated with PBS (93.3 [GSEM, 1.14] micrograms/ml). The IL-8 treatment also induced a significant influx of neutrophils, but not eosinophils, in bronchoalveolar lavage (BAL) fluid (18.3 +/- 8.8 and 30.6 +/- 8.3% in animals treated with 0.5 and 5 micrograms/kg, respectively, of IL-8 vs 3.6 +/- 0.7% in phosphate buffered saline-(PBS)-treated animals). Furthermore, we examined the effect of the thromboxane receptor antagonist S-1452 (0.01 or 0.1 mg/kg, i.p. 24 and 1 h before anesthesia) on this IL-8 induced BHR. S-1452 significantly inhibited the BHR dose-dependently (ANOVA P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bronchial hyperresponsiveness and airway neutrophil accumulation induced by interleukin-8 and the effect of the thromboxane A2 antagonist S-1452 in guinea-pigs. 772 25

In vitro work suggests that IL-10 plays a pivotal role in controlling the balance of pro- and anti-inflammatory cytokines and monocyte HLA-DR expression. In 20 patients undergoing cardiac surgery, we investigated elaboration of interleukin 10 (IL-10) and its relationship to pro- and anti-inflammatory cytokines and leucocyte expression of HLA-DR and adhesion molecules. There were small increases in pro-inflammatory cytokines (IL-1, IL-8 and tumour necrosis factor (TNF) after induction, returning to baseline on induction of cardiopulmonary bypass (CPB). After CPB another transient increase in IL-8 occurred (P < 0.05). The anti-inflammatory response began with elevated IL-10 during CPB (P < 0.001), which peaked early in recovery (P < 0.001), by which time IL-1 receptor antagonist (IL-1ra) and the TNF soluble receptors (TNFsr) had also increased (P < 0.01). The next day IL-10 and IL-1ra were decreasing but TNFsr continued to increase. Induction of anaesthesia caused HLA-DR downregulation. The IL-10 peak was associated with further monocyte HLA-DR downregulation (P < 0.001) and return towards baseline of granulocyte adhesion molecule expression which transiently increased during CPB (P < 0.001). To determine which aspects of the immune response arose from the interaction of blood with the CPB apparatus, the above variables were studied within an isolated CPB circuit and the influence of fentanyl on the magnitude of any such changes determined. Five healthy volunteers donated two, 250-ml samples of blood to which was added either fentanyl 175 micrograms with heparin 1050 u. or heparin alone 1050 u. These were used to prime two identical isolated CPB circuits and circulation was conducted under identical conditions for 90 min. Of the pro-inflammatory cytokines, only IL-8 was elevated at 90 min CPB (P < 0.05). There was no increase in anti-inflammatory cytokines and TNFsr decreased (P < 0.001). Granulocyte adhesion molecules were increased during CPB. In the fentanyl group, the CD11b increase was greater and preceded CPB. The reduction in lymphocyte HLA-DR expression, observed throughout the study period (P < 0.01), was greater with fentanyl (P < 0.05). Monocyte HLA-DR expression increased (P < 0.05), but to a lesser extent with fentanyl (P > 0.05). In contrast with the in vivo response where there was a phased anti-inflammatory response beginning with IL-10, in the isolated CPB model no anti-inflammatory cytokine response occurred.
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PMID:Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. 870 23

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

Repeated intranasal administration of interleukin 8 (IL-8) induces bronchial hyperresponsiveness (BHR) accompanied by lower airway neutrophil accumulation (ANA) in guinea-pigs. Leukotriene B4 (LTB4) is a chemotactic factor for neutrophils. To elucidate whether LTB4 and neutrophil elastase are involved in the IL-8-induced BHR and ANA, the effects of a LTB4 antagonist (ONO-4057) and a neutrophil elastase inhibitor (ONO-5046) on the responses were examined. IL-8 (5 microg x kg[-1]) was administered intranasally to guinea-pigs twice weekly for 3 weeks. One day after the last administration, animals were anaesthetized and artificially ventilated through tracheal cannulae, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to inhaled histamine. ONO-4057 (2 or 20 mg x kg[-1]) or ONO-5046 (30 or 300 mg x kg[-1]) was administered intraperitoneally 24 and 1 h before anaesthesia. ONO-4057, but not ONO-5046, significantly inhibited the IL8-induced BHR and ANA, assessed by bronchoalveolar lavage, in a dose-dependent manner. These findings suggest that interleukin 8 causes bronchial hyperresponsiveness and airway neutrophil accumulation in guinea-pigs in vivo. In part this appears to be due to release of leukotriene B4, whereas it may not be mediated by neutrophil elastase.
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PMID:Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8. 955 29

Alterations in the mononuclear cell populations in the blood circulation are among the most characteristic changes after surgical trauma. They reflect changes in the hematopoietic compartment which develop following surgery. The process of mobilization and differentiation of the hematopoietic population is regulated by cytokines known as growth factors for stem and progenitor cells (SCF, IL-1, IL-3, IL-6, IL-1L, TNF, CSFs). Our question was whether operative trauma resulted in the release of the hematopoietic progenitor cells to the blood circulation and an increase in the blood level of cytokines participating in hematopoiesis. The studies were carried out in patients with chronic cholelithiasis, undergoing elective open cholecystectomy under general anesthesia. An increase in the frequency of circulating CD34+ hematopoietic progenitor cells was seen between days 3 and 7 after surgery. Moreover, a significant increase in the percentage of immature cells of myeloid lineage (CD13+, CD14+, CD33+) was seen on the 1st and 3rd postoperative days. This could be the result of an expansion of the total bone marrow cell number after surgery and a subsequent release of these cells into the blood circulation. The changes in blood cell populations were accompanied by an increase in IL-6 on days 1, 3, and 7 following surgery, in IL-6sR on days 10 and 14 and in IL-8 on days 1 and 3. No significant changes in IL-1alpha, IL-1beta, IL-3 and IL-11 were noted. A small rise in GM-CSF was noted in few patients on the 3rd and 7th postoperative days. It is known that IL6 is involved in hematopoiesis, that the IL6-IL-6sR complex may induce both proliferation and differentiation of hematopoietic progenitor cells and that IL8 possesses progenitor cell mobilization properties. The appearance of hematopoietic progenitor cells in the blood following surgery may represent a process for the expansion of the immune cell pool after trauma and maintaining of the reserves at a certain level.
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PMID:Surgical trauma evokes a rise in the frequency of hematopoietic progenitor cells and cytokine levels in blood circulation. 962 17

The effect of cardiopulmonary bypass (CPB) on various blood parameters in children undergoing major cardiovascular surgery was investigated in a prospective clinical study. Blood samples of children with CPB (CPB group, n = 18) or without CPB (control, n = 12) were collected before, during, and after surgery. The concentration of routine laboratory parameters, components of the complement system (C3, C4, C5, C1 inhibitor, total hemolytic complement, C3d, and C5a), circulating interleukins (IL-6 and IL-8) and soluble adhesion molecules (sICAM-1 and sE-selectin) were determined. In both groups of patients the serum concentrations of C3, C4, C5, and C1 inhibitor were significantly affected by the treatments (p < 0.001), decreased immediately after onset of anesthesia, were minimal during surgery, and increased thereafter. No significant differences in the kinetics of these parameters were detectable between CPB and control group. In the CPB group the activation of the alternative pathway (increased C3d) was found to be a specific response (p = 0.005), but also in the control group C3d and C5a concentration increased significantly (p < 0.022), indicating complement activation. None of the effects that would be expected after activation of the complement system were specific for the CPB group. In both groups the serum levels of IL-6 increased dramatically during and/or after surgery (p = 0.001), and IL-8 was detectable after surgery in 10/12 control patients. The concentration of sICAM-1 and sE-selectin decreased during surgery (p < 0.04) and later did not increase above baseline. Our data suggest that increased serum levels of inflammation mediators and increased consumption of complement and adhesion molecules occur during cardiovascular surgery. Although complement activation and ICAM-1 consumption are more pronounced in the CPB patients, none of these changes occurs exclusively in the CPB group. We conclude, therefore, that these changes are the combined effect of anesthesia, surgical trauma, and endothelial lesions. Additional, undefined CPB-induced reactions may also contribute the postoperative morbidity.
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PMID:Complement activation, cytokines, and adhesion molecules in children undergoing cardiac surgery with or without cardiopulmonary bypass. 998 87

1. The purpose of this study was to determine whether shed autologous blood collected postoperatively contains complement split products (C3a and SC5b-9) and proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) and whether transfusion of shed blood increases the concentrations of inflammatory mediators in the circulation. 2. Twenty consecutive patients undergoing total hip replacement surgery under spinal anaesthesia were studied. The patients were transfused with whole blood collected postoperatively. 3. The median volume shed blood returned to the patients was 350 ml (25-75% range = 300-450). Before transfusion of shed blood was filtered using a 40 microm filter (Solcotrans). Samples for complement and cytokine determinations were drawn from the collected blood. 4. Venous blood samples were drawn 1 min before transfusion, 1 and 60 min after completed transfusion. High concentrations of C3a, SC5b-9, TNF-alpha, IL-1beta, IL-6 and IL-8 were found in shed blood. The concentrations were higher than the circulating levels (P < 0.05). The filtration procedure did not significantly reduce the concentrations. 5. Transfusion of the shed blood did not significantly alter the circulating concentrations of C3a, SC5b-9, TNF-alpha, IL-1beta, and IL-8. The plasma concentrations of IL-6 were increased both 1 and 60 min after completed transfusion compared to before (P < 0.05). 6. This study shows that whole blood collected from a surgical wound contains large concentrations of complement split products and proinflammatory cytokines. Transfusion of shed blood leads to elevated plasma levels of IL-6.
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PMID:Formation of complement split products and proinflammatory cytokines by reinfusion of shed autologous blood. 1004 32

Cardiopulmonary bypass (CPB) impairs pulmonary endothelial injury in part by increasing expression of adhesion molecules that results in neutrophil influx. Although numerous proinflammatory cytokines up-regulate these responses, the extent to which systemic and pulmonary proinflammatory cytokines increase remains unknown. We therefore examined systemic and pulmonary gene expression and production of proinflammatory cytokines during CPB. Bronchoalveolar lavage and peripheral blood sampling were performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) was measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. We also measured these cytokines in cultured alveolar macrophages and plasma monocytes in standard medium alone, or in the presence of lipopolysaccharide. We found 2- to 20-fold increases in gene expression for these cytokines in both plasma and alveolar leukocytes at the end of surgery. However, the increases were 4-8 times greater in alveolar than plasma leukocytes. Alveolar macrophages obtained at the end of surgery produced 1.5-3 times more IL-6, IL-8, and TNF-alpha than those obtained at the beginning (P < 0.0001). Although plasma monocytes produced more IL-8 at the end of surgery (P < 0.001), TNF-alpha and IL-6 did not increase. The production of all cytokines was 1.5-3 times greater in alveolar macrophages obtained at the end of surgery than in plasma monocytes obtained simultaneously (P < 0.005). Our data thus suggest that CPB provokes a greater pulmonary than systemic inflammatory response.
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PMID:Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines. 1078 50

Atelectasis is a major cause of decreased arterial oxygenation after cardiopulmonary bypass (CPB). There is a close relationship between atelectasis and inflammatory responses. We therefore tested the hypothesis that neutrophil number and the concentrations of proinflammatory cytokines and elastase in plasma and bronchoalveolar lavage fluid correlate with changes in arterial oxygenation. Bronchoalveolar lavage was performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. Peripheral blood was sampled simultaneously. Arterial oxygenation was quantified by PaO(2)/fraction of inspired oxygen (FIO(2)) and intrapulmonary shunt (Q(s)/Q(t)). PaO(2)/FIO(2) and Q(s)/Q(t) decreased significantly at the end of surgery, whereas neutrophil number, interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and elastase concentrations in the lavage fluid increased significantly. The increase in neutrophil count from the lavage fluid correlated significantly with the increases in IL-8 and elastase concentrations. The increase in neutrophil number and IL-8 and elastase concentrations in the lavage fluid correlated significantly with PaO(2)/FIO(2) and Q(s)/Q(t) at the end of surgery. In contrast, none of the plasma values correlated with these variables. Significant correlation between immune mediators and decreased arterial oxygenation suggests that inflammatory responses in the distal airway are strongly related to a decrease in arterial oxygenation after CPB.
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PMID:Neutrophil number and interleukin-8 and elastase concentrations in bronchoalveolar lavage fluid correlate with decreased arterial oxygenation after cardiopulmonary bypass. 1078 51


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