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)

Multiple insults may induce bronchopulmonary dysplasia (BPD) in premature infants, including the recently reported association of BPD with neonatal Ureaplasma urealyticum colonization. One mechanism of damage could involve stimulation of proinflammatory cytokine release from pulmonary fibroblasts. We therefore compared the effects of U. urealyticum, oxygen, and lipopolysaccharide (LPS) on the release of interleukin (IL)-1 beta, IL-6, and IL-8 from neonatal fibroblasts. Fibroblasts were grown in multiwell plates and divided into the following experimental conditions: fibroblasts alone, fibroblasts plus U. urealyticum (10,000 cfu/mL), and fibroblasts plus LPS (2 micrograms/mL). Plates were then exposed to room air or hyperoxia for 48 h, and supernatants were assayed for IL. U. urealyticum-infected fibroblasts produced a significant increase in IL-6 (P < .05) and a dramatic increase in IL-8 (P < .05) that was independent of hyperoxic exposure and significantly increased over that produced by LPS or hyperoxia alone. U. urealyticum is a potent inducer of fibroblast cytokine release in vitro and may contribute to the development of BPD.
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PMID:Induction of human neonatal pulmonary fibroblast cytokines by hyperoxia and Ureaplasma urealyticum. 839 7

The purpose of this study was to describe cytokine profiles of human neonatal pulmonary cells isolated by tracheal aspiration (TA) and by deep pulmonary lavage (DPL). We hypothesized that mRNA phenotyping, using the technique of reverse transcriptase polymerase chain reaction (RT-PCR), would reveal differences in cytokine expression patterns between cells from proximal and distal airway compartments. We reasoned that cells derived by DPL may reflect pathogenic pathways indicative for the development of bronchopulmonary dysplasia in the premature infant. Here we have described the detection of mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha. Fourteen paired TA and DPL samples from six premature infants were collected at 1, 7, or 28 d of age. Two of 14 samples were negative for beta-actin (a ubiquitous mRNA) by RT-PCR and were excluded from further analysis. Each of the remaining 12 samples expressed IL-8. Furthermore, each cytokine could be expressed by TA or DPL cells. Cytokine mRNA phenotype profiles were found to differ between TA and DPL cells in four of five paired samples. Our results show that cells retrieved from these two pulmonary compartments are sources for these cytokines and suggest that RT-PCR of TA/DPL cells can be used to test hypothetical predictive markers for the development of bronchopulmonary dysplasia.
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PMID:Differential cytokine mRNA expression by neonatal pulmonary cells. 882 95

An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has anti-inflammatory effects in asthma, a disease with many similarities with BPD. In a prospective, randomized, blinded study, we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk (> or = 75% probability) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were randomized to nebulized DSCG 20 mg (n = 13) or 2 cc NS (control, n = 13) every 6 h from Day 3 to Day 28. Lung lavage was collected on Day 3 (pre-study) and Day 7 and analyzed for cell count and differential and TNF-alpha, sTNFR1, sTNFR2, IL-1 beta, IL-1ra, and IL-8 concentrations. The groups' pre-study lavage cytokine concentrations were similar, but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group. Soluble TNF receptors were unaffected by DSCG. There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected by DSCG therapy. Three control subjects, but no DSCG-treated infants, died during the study period (p = 0.07). There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d (100% control subjects; 85% DSCG). These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD.
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PMID:Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia. 937 70

Ventilated preterm infants prone to the development of bronchopulmonary dysplasia have been shown to have increased inflammatory mediators in their tracheal aspirates. High frequency oscillatory ventilation (HFOV) is thought to be less traumatic than intermittent positive pressure ventilation (IPPV) in premature infants with surfactant deficiency, and therefore may reduce the inflammatory response in tracheobronchial aspirates. We randomized 76 premature infants requiring mechanical ventilation (birth weight 420-1830 g, median 840 g, gestational age 23 3/7 to 29 2/7 wk, median 26 4/7 to receive either an IPPV with a high rate (60-80/min) and low peak pressures, or an HFOV aiming at an optimization of lung volume, within 1 h of intubation. Tracheal aspirates were systematically collected during the first 10 d of life and analyzed for albumin, IL-8, leukotriene B4 (LTB4), and the secretory component (SC) for IgA as a reference protein. Bacterially colonized samples were excluded. On the treatment d 1, 3, 5, 7, and 10, the resulting median values of albumin (milligrams/mg of SC) were 28, 23, 24, 18, and 10, in IPPV-ventilated infants, and 33, 28, 18, 25, and 39 in HFOV-ventilated infants, respectively. Median IL-8 values (nanograms/mg of SC) were 671, 736, 705, 1362, and 1879 (IPPV) and 874, 1713, 1029, 1426, and 1823 (HFOV), respectively, and median LTB4 values (nanograms/mg of SC) were 26, 13, 27, 22, and 11 (IPPV) and 15, 12, 7, 12, and 16 (HFOV), respectively. Values were similar in IPPV- and HFOV-ventilated infants, and no significant differences were noted. We conclude that HFOV, when compared with a high rate low pressure IPPV, does not reduce concentrations of albumin, IL-8, and LTB4 in tracheal aspirates of preterm infants requiring mechanical ventilation.
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PMID:Comparison of pulmonary inflammatory mediators in preterm infants treated with intermittent positive pressure ventilation or high frequency oscillatory ventilation. 972 9

A borderline viability model of bronchopulmonary dysplasia (BPD)/chronic lung disease of infancy (CLD) with pathophysiologic parameters consistent with those in extremely immature humans with BPD/CLD is described. After prenatal steroid treatment of pregnant dams, 12 premature baboons were delivered by cesarean-section at 125 d (term gestation, 185 d), treated with exogenous surfactant, and maintained on appropriate oxygen and positive pressure ventilation for at least 1 to 2 mo. In spite of appropriate oxygenation (median FI(O(2)) at 28 d = 0.32; range, 0.21 to 0.50) and ventilatory strategies to prevent volutrauma, the baboons exhibited pulmonary pathologic lesions known to occur in extremely immature humans of less than 1,000 g: alveolar hypoplasia, variable saccular wall fibrosis, and minimal, if any, airway disease. The CLD baboon lungs showed significantly decreased alveolization and internal surface area measurements when compared with term and term + 2-mo air-breathing controls. A decrease in capillary vasculature was evident by PECAM staining, accompanied by dysmorphic changes. Significant elevations of TNF-alpha, IL-6, IL-8 levels, but not of IL-1beta and IL-10, in tracheal aspirate fluids were present at various times during the period of ventilatory support, supporting a role for mediator-induced autoinflammation. IL-8 levels were elevated in necropsy lavages of animals with significant lung infection. This model demonstrates that impaired alveolization and capillary development occur in immature lungs, even in the absence of marked hyperoxia and high ventilation settings.
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PMID:Neonatal chronic lung disease in extremely immature baboons. 1050 26

The mechanism by which dexamethasone (DEX) inhibits neutrophil (PMN) recruitment to a site of inflammation, such as the newborn lung with bronchopulmonary dysplasia, is not completely understood. The aim of our study was to determine whether DEX inhibits neutrophil-induced neutrophil recruitment by inhibition of interleukin- (IL) 8 release from PMNs, and if there are developmental differences. PMNs isolated from cord blood (CB) and adults (A) were studied. We first measured the effect of DEX (10(-10) to 10(-4) M) on PMN migration to an exogenous IL-8 standard (10(-8) M) using PMNs of CB (n = 3) and A (n = 3), over 1 h in a chemotaxis chamber. Second, we determined the effect of DEX (0 and 10(-10) to 10(-6) M) on IL-8 release (immunoassay) from PMNs of CB (n = 7) or A (n = 7) after incubation with lipopolysaccharide (LPS, 1 ng/mL) for 6 and 18 h. Third, the chemoattractant activity of culture media from the second experiment was studied with and without IL-8 antibody. DEX at concentrations of 10(-10) to 10(-4) M had no direct effect on PMN migration in vitro to an exogenous IL-8 standard. After LPS exposure, IL-8 release was greatly increased for PMNs from CB compared with A. DEX (10(-10) to 10(-4) M) resulted in a dose-dependent inhibition of IL-8 release from PMNs exposed to LPS for 6 and 18 h incubation. Increased PMN migration activity was only found with media of PMNs of CB with no DEX. At 18 h, media-induced migration activity was decreased if DEX (10(-7) M), IL-8 antibody, or DEX (10(-7) M) with IL-8 antibody were present during the incubation with LPS: there was an 88, 86, and 101% reduction in migration activity, respectively. We conclude that DEX inhibits PMN-induced PMN migration, predominantly via inhibition of IL-8 release for PMNs of the newborn. We suggest that a 10-fold lowering of the standard DEX dose may effectively reduce lung inflammation in bronchopulmonary dysplasia.
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PMID:Mechanism for dexamethasone inhibition of neutrophil migration upon exposure to lipopolysaccharide in vitro: role of neutrophil interleukin-8 release. 1050 60

The objective of this study was to determine the doses of dexamethasone (DEX), betamethasone (BET), and hydrocortisone (HC) that effectively inhibit the release of two potent proinflammatory chemokines, interleukin 8 (IL-8) and macrophage inflammatory protein alpha (MIP), from polymorphonuclear neutrophils (PMNs) of the newborn. Human PMNs were isolated from cord blood (n = 18). Chemokines were measured from PMN cell culture supernatants after 18 h of stimulation using tumor necrosis factor (1 ng/ml), with and without pretreatment by DEX (10(-10) to 10(-6) M) versus HC or BET (10(-10) to 10(-5) M). Maximal inhibitions of IL-8 release by BET, DEX, and HC were 97, 91, and 91%, respectively. For MIP, the maximal inhibitions by BET, DEX, and HC were 88, 69, and 70%, respectively. The 50% inhibitory concentrations by DEX, BET, and HC for IL-8 release were 3.4 +/- (SE) 1.6 x 10(-9), 1.8 +/- 7.4 x 10(-8), and 1.8 +/- 0.5 x 10(-7) M, respectively. The 50% inhibitory concentrations by DEX, BET, and HC for MIP release were 1.0 +/- (SE) 0.5 x 10(-8), 3.8 +/- 3.1 x 10(-8), and 4.8 +/- 1.6 x 10(-7) M, respectively. In vitro, these corticosteroids effectively inhibited the release of two structurally different chemokines that are found in the airway lavage fluids of infants developing bronchopulmonary dysplasia. When compared to plasma DEX levels previously reported during the treatment of bronchopulmonary dysplasia, our results suggest that the doses of DEX, and potentially BET, needed to treat chronic lung disease may be more than five to ten times lower than those of current DEX regimens.
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PMID:Dose-related inhibition of proinflammatory cytokine release from neutrophils of the newborn by dexamethasone, betamethasone, and hydrocortisone. 1216 30

Macrophage-derived cytokines may provoke the inflammatory response in lung injury. Because macrophage influx is a prominent feature of the cellular inflammatory response accompanying the development of bronchopulmonary dysplasia, we hypothesized that blocking macrophage influx would reduce overall cellular influx and oxidative damage. Newborn rats were exposed at birth to 95% O(2) or air for 1 wk, and hyperoxia-exposed pups were injected with anti-monocyte chemoattractant protein-1 (MCP-1) or IgG control on days 3-5. MCP-1 was increased in bronchoalveolar lavage fluid and in histological sections from the 95% O(2)-exposed, IgG-injected pups compared with air-exposed controls. At 1 wk, anti-MCP-1-treated pups had reduced leukocyte numbers, both macrophages and neutrophils, in bronchoalveolar lavage fluid compared with IgG-treated controls. Cytokine-induced neutrophil chemoattractant-1, the rat analog of IL-8, was not significantly decreased in lavage fluid but was reduced in lung cells in anti-MCP-1-treated pups. Tissue carbonyls, a measure of protein oxidation, were decreased in anti-MCP-1-treated pups. Anti-MCP-1 treatment prevented neutrophil influx and reduced protein oxidation in hyperoxia-exposed newborn rats.
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PMID:Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung. 1258 6

An increase in polymorphonuclear leukocytes (PMNs) and proinflammatory chemokines, such as IL-8 and macrophage inflammatory protein-1 alpha (MIP), are found in the airways during early stages of bronchopulmonary dysplasia. We determined whether IL-10 produces a dose-related inhibition of proinflammatory chemokine release from stimulated neutrophils of the newborn and whether the mechanism involves the pivotal transcription factor, nuclear factor-kappa B. PMNs isolated from the cord blood of healthy newborns were stimulated submaximally with either lipopolysaccharide (n = 5) or tumor necrosis factor (n = 4), with and without IL-10 (0.01-1000 ng/mL). IL-8 and MIP release were measured in cell culture supernatants at 18 h. The presence or absence of nuclear factor-kappa B activity and inhibitor-kappa B alpha degradation was measured at 30 min and 3 h after PMN stimulation began. During lipopolysaccharide stimulation, IL-10 significantly reduced IL-8 levels from 50 +/- 16 ng/mL to 7 +/- 3 ng/mL, and MIP levels from 14 +/- 5 to 0.7 +/- 0.1 ng/mL (mean +/- SEM, p < 0.01). IL-10 produced an insignificant reduction in IL-8 and MIP levels after stimulation of PMNs with tumor necrosis factor. IL-10 did not inhibit nuclear factor-kappa B activation and inhibitor-kappa B alpha degradation in PMNs stimulated with tumor necrosis factor or lipopolysaccharide for 30 min. After PMN stimulation for 3 h, inhibitor-kappa B alpha cytoplasmic levels were restored; however, they were unaffected by IL-10. We conclude that IL-10 is a potent inhibitor of lipopolysaccharide-stimulated release of IL-8 and MIP from neutrophils of the newborn via a mechanism not involving nuclear factor-kappa B activity. Further work is needed to determine whether exogenous IL-10 may be useful for suppressing inflammation in bronchopulmonary dysplasia.
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PMID:Interleukin-10 inhibits proinflammatory chemokine release by neutrophils of the newborn without suppression of nuclear factor-kappa B. 1278 80

Current nonhuman models for bronchopulmonary dysplasia have not included perinatal infection. We studied the effects of antenatal Ureaplasma urealyticum (Uu) infection in the 125-d immature baboon. Ten 125-d gestation (term = 185 d) baboon dams were delivered after intra-amniotic inoculation with Uu. Serial blood and tracheal aspirate samples were analyzed for Uu colony-forming units, IL-6, IL-8, and cell counts. Physiologic parameters were serially recorded. Lung histology was examined after 14 d of ventilation and compared with unexposed controls. All Uu-exposed animals had >4 x 102 CFU in tracheal aspirate at 24 h. Four of nine Uu animals remained heavily colonized [(+) Uu] at necropsy (>6 x 103). Five animals had negative or low tracheal colony-forming units. All Uu animals had significant increases for white blood cells, IL-6, and IL-8 in amniotic and fetal lung fluid. Compared with controls, (+) Uu animals had significantly higher fraction of inspired oxygen, airway pressures, oxygenation index, and ventilation efficiency index between 48 and 240 h and had significantly elevated tracheal IL-6 and IL-8 concentrations between 72 and 240 h. Compared with controls (-) Uu animals had significantly better oxygenation index and ventilation efficiency index scores between 48 and 144 h. Lung histopathology in both Uu groups showed more severe bronchiolitis and interstitial pneumonitis compared with controls. Two patterns of disease were observed after Uu perinatal infection. Persistent colonization manifested a picture consistent with acute pneumonitis, worse lung function from 2 to 10 d, and prolonged elevated tracheal cytokines. Colonized animals that subsequently cleared Uu from the lung demonstrated early improved lung function compared with unexposed controls yet still manifested mixed bronchiolitis and interstitial pneumonitis at necropsy. Inherent immune system responses may determine outcome of perinatal Ureaplasma colonization.
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PMID:Effects of antenatal colonization with ureaplasma urealyticum on pulmonary disease in the immature baboon. 1293 Sep 7


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