UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to search for early inflammatory mediators in severely traumatized patients that could predict the occurrence of adult respiratory distress syndrome (ARDS). We measured sequential plasma levels of tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), complement fragment C3a, and endotoxin. In addition, we measured sequentially the values of hemodynamics, oxygen transport, and pulmonary function. The temporal patterns seen in the patients who developed ARDS were compared with those who did not. In the patients who developed ARDS, the first observed findings were low cardiac index (CI) and oxygen delivery (DO2) followed by progressive increases in IL-6, IL-8 and C3a levels, worsening of pulmonary function, and increases in hemodynamic values. The maximum values of IL-6, IL-8, and C3a occurred after the onset of ARDS. In the patients who did not develop ARDS, initial oxygen transport values were not low, the levels of IL-6, IL-8, and C3a decreased rapidly from their initial peaks, and there were no further increases in hemodynamic values. In both ARDS and nonARDS patients, no measurable quantities of TNF, IL-1, or endotoxin were found. We concluded that none of the mediators we measured reached their peaks before the onset of ARDS and none were found to be predictive of posttraumatic ARDS. However, these and other mediators may augment or intensify the development of ARDS.
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PMID:Temporal patterns of hemodynamics, oxygen transport, cytokine activity, and complement activity in the development of adult respiratory distress syndrome after severe injury. 818 65

Cytokine treatment in patients with myelodysplastic syndrome (MDS) aims to overcome the maturation defects of myeloid lineage cells associated with cytopenia and cellular dysfunction of mature cells. Since phagocytes play a major role in host defense against microbial infection, we investigated cytokine secretion and oxygen radical release (ORR) from peripheral blood monocytes (PBMC) in a total of 16 MDS patients, 12 patients with refractory anemia (RA) and four patients with RA and excess of blasts (RAEB). Interleukin (IL-6), tumour necrosis factor alpha (TNF alpha), IL-1 beta, and IL-8 secretion from monocytes in response to lipopolysaccharide (LPS) was significantly reduced in the 12 patients with RA compared to 12 healthy controls, whereas no difference was seen in ORR. We further assessed cytokine secretion from monocytes of 10 MDS patients before and after therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or a combination therapy with GM-CSF and cytosine arabinoside (AraC). In all 10 patients, secretion of IL-1 beta, IL-6, and TNF alpha from PBMC increased after cytokine therapy, whereas IL-8 secretion increased only in five patients with GM-CSF or IL-3 therapy receiving a dosage > or = 250 micrograms/m2 per day but decreased in all other patients. ORR increased in all patients on either GM-CSF or IL-3 therapy. These data indicate that the ability of monocytes to secrete secondary cytokines is impaired in MDS patients but can be restored by in vivo administration of GM-CSF and IL-3.
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PMID:Restoration of impaired cytokine secretion from monocytes of patients with myelodysplastic syndromes after in vivo treatment with GM-CSF or IL-3. 823 Dec 42

Bactericidal/permeability-increasing protein (BPI) is a major component of the granules of polymorphonuclear neutrophils (PMNs) and is involved in the killing of gram-negative bacteria. A 23-kd recombinant protein, corresponding to the NH2-terminal fragment of human BPI (rBPI23), has been shown to bind lipid A and antagonize some lipopolysaccharide (LPS)-mediated effects. In this study the ability of rBPI23 to prevent a wide range of cellular responses to LPS was investigated. In vitro assays were carried out using human blood to more closely approximate in vivo conditions. The release of proinflammatory cytokines [tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), IL-6, IL-8], induced by E. coli O113 LPS, was markedly reduced by rBPI23 in a concentration-dependent fashion. The production of the anti-inflammatory protein IL-1ra (IL-1 receptor antagonist) was triggered by lower LPS concentrations than those necessary for the other cytokines. Furthermore, prevention of IL-1ra release required higher rBPI23 concentrations than for other cytokines. The LPS-induced production of oxygen-derived free radicals by phagocytic cells (resulting in chemiluminescence) was also prevented by rBPI23. The inhibition was specific for LPS because the activation of leukocytes by phorbol myristate acetate, zymosan, or TNF was unaffected by BPI. The ability of rBPI23 to antagonize specifically the effects of endotoxin in the complex environment of human blood along with its bactericidal activity suggests that rBPI23 may be a novel therapeutic agent in the treatment of gram-negative infections.
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PMID:A recombinant amino terminal fragment of bactericidal/permeability-increasing protein inhibits the induction of leukocyte responses by LPS. 824 7

Reactive oxygen intermediates (ROIs) are involved in many neurological diseases. Despite the toxic nature of these compounds, low concentrations of ROIs can function as signaling molecules. One target for their signaling function is the inducible transcription factor NF-kappa B. Predominantly in lymphoid cells, induction of NF-kappa B in response to oxidative stress leads to transcriptional activation of many genes which are relevant for pathogen defense. These include the TNF, IL-6, IL-8, GM-CSF, beta-interferon, MHC class I and V-CAM genes. However, NF-kappa B is also abundant in various cell types of the nervous system, including neurons. We propose that NF-kappa B plays a role as a redox-controlled transcriptional activator also in cells of the nervous system and in that property may contribute to neurological disorders. Our finding that some neurons from healthy brain contain constitutively active NF-kappa B suggests a role of NF-kappa B in normal brain function as well.
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PMID:Potential involvement of the transcription factor NF-kappa B in neurological disorders. 826 32

Historically, the neutrophil has been perceived as a terminally differentiated leukocyte with limited ability to produce de novo proteins. Furthermore, in the context of acute inflammation the activated neutrophil has been appreciated only for its ability to release various proteases, reactive oxygen, and arachidonic acid metabolites. Recently, the neutrophil has been shown to have the capacity to produce a number of cytokines that may be instrumental in orchestrating the progression of acute inflammation to a more chronic and specific immune response. These cytokines include IFN-alpha, M-CSF, G-CSF, TNF, IL-1, and IL-6. Our laboratory and others have shown that neutrophils produce IL-8 in response to LPS or a phagocytic challenge. Although these studies have shown the induction of IL-8 from polymorphonuclear neutrophils (PMN), relatively little is known regarding the regulation of PMN-derived IL-8. Because PMN and monocytes share the same stem cell, and monocyte-derived IL-8 is regulated by prostaglandin E2 (PGE2), glucocorticoids (dexamethasone; DEX) and the T-Lymphocyte-derived IL-4, we postulated that PMN-derived IL-8 production may be regulated in a similar manner. To test this hypothesis, PMN were isolated (> 99% pure) from peripheral blood and cultured in media with 5% FCS in the presence or absence of LPS (10 ng/ml; a concentration of LPS that induced the half-maximal production of PMN-derived IL-8) and in the presence or absence of DEX (10(-6) M to 10(-10) M), PGE2 (10(-6) M to 10(-10) M), or IL-4 (100 ng/ml to 100 pg/ml). PMN-derived IL-8 was measured using a specific sandwich ELISA. DEX and IL-4 in the presence of LPS were found to inhibit PMN-derived IL-8 in both a dose- and time-dependent fashion. DEX and IL-4 in concentrations of 10(-6) M and 10 ng/ml resulted in maximal inhibition of LPS-induced PMN-derived IL-8, respectively. Moreover, both DEX and IL-4 administration could be delayed 4 hr post-stimulation with LPS and result in significant suppression of PMN-derived IL-8. Interestingly, in contrast to the regulation of monocyte-derived IL-8 by PGE2, PGE2 treatment of PMN failed to inhibit the generation of LPS-induced IL-8. Northern blot analysis of steady-state IL-8 mRNA demonstrated that both DEX and IL-4 treatment of PMN resulted in a 40 and 52% reduction in LPS-stimulated PMN-derived IL-8 mRNA, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of neutrophil-derived IL-8: the role of prostaglandin E2, dexamethasone, and IL-4. 834 1

Prognosis in myelodysplastic syndrome (MDS) is not only correlated closely with blast cell count in bone marrow and chromosomal abnormalities but also correlated with decreased leucocyte count and function leading to acquisition of lethal infections. Recently, clinical trials in MDS have focused on the application of haemopoietic growth factors such as G-CSF or GM-CSF, which have proven to increase neutrophil count and function. However, these cytokines carry the risk of stimulating the malignant clone, particularly in patients with increased blast cell count. Therefore, investigation of cytokines which are able to stimulate neutrophil function without the potential risk of stimulating haemopoietic progenitor cells may be relevant for MDS. As the stimulatory effect of interleukin-8 on neutrophil function is well known, we investigated whether recombinant human IL-8 is also able to improve the function of neutrophils gained from patients with MDS. Using three different techniques--the E. coli killing assay (8 patients), the production of reactive oxygen as determined by cytochrome c reduction (7 patients) and chemiluminescence (8 patients)--a significant stimulation of neutrophil function at a concentration of 10 nm IL-8 was found in all test systems. No correlation with FAB classification was evident. On the other hand, IL-8 only mildly stimulated growth of myeloid progenitor cells in bone marrow culture of healthy individuals and MDS patients. This minimal stimulation was blocked by a neutralizing antibody directed against GM-CSF, suggesting an indirect effect of IL-8 via secondary GM-CSF release. Thus, IL-8 is able in vitro to repair the functional abnormalities of neutrophils from patients with MDS but has only a marginal influence on myeloid progenitor cells.
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PMID:Recombinant human interleukin-8 restores function in neutrophils from patients with myelodysplastic syndromes without stimulating myeloid progenitor cells. 838 40

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

Sleep related breathing disorders influence the structure of sleep by considerably modifying the ratios of the individual sleep stages. The sleep analyses carried out by polysomnography in the diagnosis of sleep related breathing disorders have so far been evaluated manually according to the criteria of Rechtschaffen and Kales, since automatic systems do not permit standardised evaluation as yet. Automatic sleep analyses via SAC, however, has been developed further in recent years and has widened its scope and efficiency. It is now possible to perform a comprehensive sleep analysis via SAC by means of modified criteria after Rechtschaffen and Kales. The SAC determines individual curves in the EEG and EOG and includes in addition to the EEG parameters an automatic apnoea detection as well as detailed breathing and oxygen saturation analyses. The Sleep Analysis Computer (SAC) records 15 parameters (2 EEG, 2 EOG, 2 EMG, ECG, NAF, thoracic and abdominal breathing curves, oxygen saturation, body posture, optionally blood pressure = RR, CPAP etc.). This means that all the parameters required for diagnosing sleep related breathing disorders as well as their differential diagnosis can be determined. Within the framework of a blood pressure study, 16 patients (average 45.5 SD 4.6 years) were subjected to SAC measurement in addition to conventional PSG. The computer recordings were evaluated according to apnoea index, the form of the apnoea and the oxygen saturation desaturations. The evaluation yielded the following pattern: 4 patients with AI < 10, 8 patients with AI between 10 and 20, 4 patients with AI > 20. Obstructive apnoeas were seen in 6 patients, mixed apnoeas in 8 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Sleep analysis computer in diagnosis of sleep-related respiratory disorders]. 849 65

Polymorphonuclear neutrophils (PMN) are known to participate in the development of tissue injury during myocardial infarction due to both free oxygen radicals release, as well as to their involvement in the "no-reflow" phenomenon. We have previously shown that peripheral blood plasma (obtained from patients with acute myocardial infarction) has chemotactic activity for PMN and is able to induce PMN adherence as well as superoxide anion production. To investigate whether interleukin-8 (IL-8/NAP-1), a potent chemotactic factor for PMN, is involved in plasma-mediated PMN stimulation, we measured plasma levels of IL-8 in five patients with transmural myocardial infarction with highly sensitive enzyme-linked immunosorbent assay (ELISA) using specific antibodies. Blood samples were taken immediately after patients' admission, within 15 and 30 min of treatment with intravenous nitrates, as well as after 1, 2, 3, and 7 days. All samples expressed IL-8 activity within the detection limit (0.4 ng/ml) as observed at the basal state. Thus, IL-8 may not be considered as responsible for the chemotactic activity in peripheral blood in patients with myocardial infarction.
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PMID:Interleukin-8 is not involved in the increased chemotactic activity of peripheral blood plasma during acute myocardial infarction. 850 32

Cytokine networks between immune and nonimmune cells of the alveolar-capillary membrane are necessary for cellular communication during pulmonary inflammation. The subsequent events of these cellular/humoral interactions are pivotal to the initiation and propagation of the inflammatory response leading to pulmonary injury. The studies cited in this paper underscore the interrelationship of early response cytokines, adhesion molecules, and the chemokine IL-8 that orchestrate the recruitment of neutrophils into the lung. The paradigm for neutrophil extravasation is likely operative in the microvasculature of the lung, and consists of four or more steps (Figure 3). First, acute lung injury results in the activation of microvascular endothelium in response to the local generation of TNF or IL-1, leading to expression of endothelial cell-derived E- and P-selectins and ICAM-1. The constitutive presence of neutrophil-derived L-selectin allows for the initial adhesive interaction of neutrophils with endothelial cell selectins leading to the "rolling" effect. Second, generation of IL-8 leads to the activation of neutrophils in the vascular compartment and expression of beta 2 integrins, while L-selectin is concomitantly shed. Third, the interaction of the neutrophil beta 2 integrin with its receptor/ligand, ICAM-1, results in the rapid arrest of neutrophils on the endothelium. Fourth, the subsequent events leading to neutrophil extravasation beyond the vascular compartment are dependent upon a combination of haplotaxis (migration in response to an insoluble gradient), the continued expression of beta 2 integrins on neutrophils and ICAM-1 on nonimmune cells, and the maintenance of a neutrophil specific (IL-8) chemotactic gradient. The participation of IL-8 and potentially other C-X-C chemokines in the inflammatory response appears to be critical for the orchestration of the directed migration of inflammatory leukocytes into the lung. After arriving in the lung, these activated leukocytes can respond to noxious stimuli or induce pulmonary injury through the release of reactive oxygen metabolites, proteolytic enzymes, and additional cytokines. Our current knowledge and future investigations regarding the mechanisms involved in neutrophil elicitation may allow us to employ clinical interventional strategies that will attenuate neutrophil-dependent acute lung injury, such as ARDS.
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PMID:Acute lung injury: the role of cytokines in the elicitation of neutrophils. 852 Oct 27

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