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

Conflicting data on the role of interleukin-2 in the recruitment of eosinophil granulocytes (EOS) to sites of inflammation have been presented. The objective of the present study was to investigate the effect of recombinant human IL-2 and anti-IL-2 on the migration of purified blood EOS. Neutralizing antibodies to IL-2 were added to a cytokine mixture with significant eosinophil chemotactic activity (ECA), and afterwards the ECA was tested on EOS from both normal and allergic donors. EOS migration was measured by a modification of the Boyden technique, using a 48-well microchemotaxis chamber. Recombinant human IL-2 was either added to the lower compartment of the chemotaxis chamber, or to the EOS for a pre-incubation period of 20 min, before migration assays towards the chemotaxins were performed. Anti-IL-2 caused a significant increase of EOS migration towards the cytokine mixture. Pre-incubation of the EOS with rhIL-2 inhibited the chemotaxis towards RANTES, PAF, IL-8 and eotaxin, and EOS migration towards IL-2 was lower than that towards buffer. These effects were more pronounced on EOS from normal than from allergic donors. Priming of the EOS with IL-5 prevented the inhibitory effect of IL-2. We hypothesize that IL-2 acts as an autocrine regulator of EOS migration, and that this inhibitory effect may be downregulated in allergy, allowing an increased migration of EOS towards chemotactic factors.
 ...
PMID:Interleukin-2 inhibits eosinophil migration but is counteracted by IL-5 priming. 1125 26

During the late-phase asthmatic response eosinophils and neutrophils infiltrate the lungs and cause severe damage. In this study, we investigated in vitro the migration of eosinophils, in the absence and presence of neutrophils, across a monolayer of lung H292 epithelial cells. The migration of eosinophils towards the complement fragment 5a (C5a) was increased when neutrophils were added to the upper compartment of the Transwells, and decreased when neutrophils were added to the lower compartment. Moreover, neutrophils exclusively stimulated eosinophil migration towards C5a, and not towards other chemoattractants such as RANTES, IL-8 or PAF. Neutrophils and eosinophils differed in that neutrophils, but not eosinophils, rapidly inactivated C5a, suggesting that neutrophils in the upper compartment remove part of the active C5a that has diffused into the upper compartment. Indeed, we found that the addition of other C5a-degrading agents, such as human serum or carboxypeptidase B, also enhanced eosinophil migration when added to the upper compartment and decreased migration when added to the lower compartment. Taken together, these results indicate that the presence of neutrophils influences the migratory behaviour of eosinophils in vitro. The neutrophils presumably maintain a proper C5a chemotactic gradient in the transmigration model, which results in enhanced eosinophil chemotaxis.
 ...
PMID:Neutrophils enhance eosinophil migration across monolayers of lung epithelial cells. 1126 Jan 57

Multi-organ dysfunction syndrome (MODS) is the primary cause of morbidity and mortality in acute pancreatitis. Recent studies have established the critical role played by inflammatory mediators such as TNFalpha, IL-1beta, IL-6, IL-8, CINC/GROalpha, PAF, IL-10, C5a, ICAM-1 and substance P in acute pancreatitis and the resultant MODS. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage, when anti-inflammatory therapy may be of use. Elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors may make it possible to develop clinically effective anti-inflammatory therapy.
 ...
PMID:Inflammatory mediators as therapeutic targets in acute pancreatitis. 1156 5

Activation of circulating neutrophils has been observed following challenge of horses with chronic obstructive pulmonary disease (COPD) and may facilitate the accumulation of these cells in the airways. In this study, no significant difference was observed between adherence to protein coated plastic of blood neutrophils from asymptomatic COPD-susceptible and normal horses stimulated by the mediators PAF, human recombinant (hr)IL-8 and hrC5a. Twenty-four hours after the start of a 7 h antigen challenge, adherence of unstimulated neutrophils from COPD-susceptible horses increased from 2.5 (0.5-4.1)% and 3.4 (0.6-6.6)% to 19.6 (16.9-20.3)% and 21.8 (10.6-23.1)% adherence for cells in medium containing 0.1% or 0.2% BSA, respectively; (median [range]; n = 4). Adherence of cells from normal horses remained unchanged. Addition of an anti-CD18 monoclonal antibody, H20A, inhibited the increase in adherence at 24 h by 96 (45-100)%, n = 3. The percentage of neutrophils in bronchoalveolar lavage fluid at 24 h increased from 1 (0-2) to 80 (65-94), (median (range), n = 4). These results suggest that antigen challenge results in exposure of circulating equine neutrophils to one or more factors that prime, or activate, these cells, which may enhance their recruitment to the lungs. Inhibition of circulating neutrophil activation may therefore represent a therapeutic target.
 ...
PMID:Antigen challenge increases adherence of circulating neutrophils in horses with chronic obstructive pulmonary disease. 1181 53

The neutrophil (PMN) is regarded as a key component in the hyperinflammatory response known as the systemic inflammatory response syndrome. Acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF) are related to the severity of this hyperinflammation. ICU patients who are at highest risk of developing MOF may have acute hypoxic events that complicate their hospital course. This study was undertaken to evaluate the effects of acute hypoxia and subsequent hypoxemia on circulating PMNs in human volunteers. Healthy subjects were exposed to a changing O2/N2 mixture until their O2 saturation (SaO2) reached a level of 68% saturation. These subjects were then exposed to room air and then returned to their baseline SaO2. PMNs were isolated from pre- and post-hypoxemic arterial blood samples and were then either stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or PMA alone, or they were primed with L-alpha-phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF) followed by fMLP activation. Reactive oxygen species generation as measured by superoxide anion production was enhanced in primed PMNs after hypoxemia. Protease degranulation as measured by elastase release was enhanced in both quiescent PMNs and primed PMNs after fMLP activation following the hypoxemic event. Adhesion molecule upregulation as measured by CD11b/CD18, however, was not significantly changed after hypoxemia. Apoptosis of quiescent PMNs was delayed after the hypoxemic event. TNFalpha, IL-1, IL-6, and IL-8 cytokine levels were unchanged following hypoxemia. These results indicate that relevant acute hypoxemic events observed in the clinical setting enhance several PMN cytotoxic functions and suggest that a transient hypoxemic insult may promote hyperinflammation.
 ...
PMID:Acute hypoxemia in humans enhances the neutrophil inflammatory response. 1195 25

Into treatment of idiopathic inflammations of the gut cytokines or their antagonists entered less than 5 years ago and they extended the range of classical medicamentous treatment with aminosalicylates, corticosteroids and immunosuppressives. The theoretical models of their therapeutic application pertained to the blocking of anti-inflammatory cytokines (IL-1, IL-6, IL-8, TNF alpha), the use of immunomodulating cytokines (IL-2, IL-6, IL-8, IL-9) similarly as the therapeutic administration of cytokines with a predominant growth and regulating activity (CSF, TGFalpha, TGFbeta, ODGF, IL-10, IL-11, IL-12). The range is supplemented by ICAM, VCAM antibody oligonucleotides and PAG antagonists. The stage of animal experiments was so far passed only by rhuIL-10, antiIL-2 and PAF antagonists. The only anticytokine which within the record time of 10 years found clinical indication in Crohn's disease, is antiTNF.
 ...
PMID:[Anti-cytokines in the treatment of idiopathic intestinal inflammations--theory and practice]. 1213 66

The lipid mediator PAF plays an important role in the phagocytosis of particles, including bacteria, and consequent production of pro-inflammatory cytokines, such as TNF-alpha and IL-8. Using a PAF receptor antagonist (UK-74,505) and PAF receptor knock-out mice, we have investigated the relevance of PAF for the inflammatory changes and lethality after pulmonary infection with the gram-negative bacteria Klebsiella pneumoniae in mice. At an inoculum of 3 x 10(6) bacteria, there was marked pulmonary (bronchoalveolar lavage and lung) neutrophilia that started early (2.5 h after infection) and peaked at 48 h. All animals were dead by day 4 of infection. The chemokine KC and the pro-inflammatory cytokine TNF-alpha increased rapidly and persisted for 48 h in the lungs. Pretreatment with UK-74,505 (30 mg kg(-1) per day, p.o.) had no significant effects on the number of infiltrating neutrophils in BAL fluid or lung tissue, as assessed by histology and measuring myeloperoxidase, or on the concentrations of KC. In contrast, concentrations of TNF-alpha and the number of bacteria inside neutrophils were significantly diminished. In order to support a role for the PAF during K. pneumoniae infection, experiments were also carried out in PAFR-deficient mice. In the latter animals, lethality occurred earlier than in wild-type controls. This was associated with greater number of bacteria in lung tissue and diminished percentage of neutrophils containing bacteria in their cytoplasm. Our results suggest that PAF, acting on its receptor, plays a protective role during infection with K. pneumoniae in mice.
 ...
PMID:Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria. 1238 75

Epinastine is a potent antiallergic agent that has not only antihistaminic (H(1)) properties but also provides antileukotriene, anti-PAF and antibradykinin activities, which are associated with its antiallergic actions. Moreover, epinastine is very effective in inhibiting the release of chemical mediators from mast cells exposed to antigen. In addition, IL-8 release from eosinophils was inhibited by epinastine posttranscriptionally. Chemotatic movement of eosinophils was also blocked by epinastine. The increase in EEG power spectrum at low frequency region detected at frontal cortex is associated with drowsiness. No such change was induced by epinastine, while a marked increase was observed after ketotifen. In agreement with this, when the amount of H(1) blockers that penetrated through the BBB into the brain was estimated by means of PET, it was apparent that epinastine hardly penetrated the BBB. With regard to the current-voltage relationship of HERG currents, epinastine did not affect I(Kr), while a marked inhibition was seen after terfenadine or astemizole. These results indicated that epinastine does not suppress delayed rectifier potassium current of the heart and, consequently, no cardiotoxic action of epinastine was postulated. In man, epinastine is readily absorbed after oral administration and no significant change in pharmacokinetics was found during chronic administration. In teratological studies in rats, malformation and variation were not observed even at high doses of epinastine. In the clinical application of epinastine, it was shown that this drug is remarkably effective in the treatment of various dermatological diseases, such as chronic urticaria, psoriasis vulgaris and other pruritic dermatoses. Moreover, epinastine provides excellent clinical efficacy in the treatment of allergic rhinitis. Although efficacy of H(1) blockers in bronchial asthma is somewhat doubtful, the overall improvement rate in asthmatic patients was significantly higher in epinastine-treated patients (53.7%) compared to those treated with ketotifen (25%).
 ...
PMID:Epinastine: An update of its pharmacology, metabolism, clinical efficacy and tolerability in the treatment of allergic diseases. 1284 34

Acute pancreatitis is a common clinical condition. The exact mechanisms by which diverse etiological factors induce an attack are unclear but once the disease process is initiated, common inflammatory and repair pathways are invoked. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked, this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicemia, severe burns and trauma. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage in acute pancreatitis, when anti-inflammatory therapy may be of use. Recent studies conducted by us and other investigators have established the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, CINC/GRO-alpha, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, and Substance P in acute pancreatitis and the resultant MODS. It is reasonable to speculate that elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors will make it possible to develop a clinically effective anti-inflammatory therapy.
 ...
PMID:Novel therapeutic targets for acute pancreatitis and associated multiple organ dysfunction syndrome. 1456 Nov 81

1. Neutrophils are thought to play a major role in the mediation of reperfusion injury. CXC chemokines are known inducers of neutrophil recruitment. Here, we assessed the effects of Repertaxin, a novel low molecular weight inhibitor of human CXCL8 receptor activation, on the local, remote and systemic injuries following intestinal ischaemia and reperfusion (I/R) in the rat. 2. Pre-incubation of rat neutrophils with Repertaxin (10(-11)-10(-6) m) inhibited the chemotaxis of neutrophils induced by human CXCL8 or rat CINC-1, but not that induced by fMLP, PAF or LTB(4), in a concentration-dependent manner. Repertaxin also prevented CXCL8-induced calcium influx but not CXCL8 binding to purified rat neutrophils. 2. In a model of mild I/R injury (30 min of ischaemia and 30 min of reperfusion), Repertaxin dose-dependently (3-30 mg kg(-1)) inhibited the increase in vascular permeability and neutrophil influx. Maximal inhibition occurred at 30 mg kg(-1). 4. Following severe I/R injury (120 min of ischaemia and 120 min of reperfusion), Repertaxin (30 mg kg(-1)) markedly prevented neutrophil influx, the increase in vascular permeability both in the intestine and the lungs. Moreover, there was prevention of haemorrhage in the intestine of reperfused animals. 5. Repertaxin effectively suppressed the increase in tissue (intestine and lungs) and serum concentrations of TNF-alpha and the reperfusion-associated lethality. 6. For comparison, we also evaluated the effects of an anti-CINC-1 antibody in the model of severe I/R injury. Overall, the antibody effectively prevented tissue injury, systemic inflammation and lethality. However, the effects of the antibody were in general of lower magnitude than those of Repertaxin. 7. In conclusion, CINC-1 and possibly other CXC chemokines, acting on CXCR2, have an important role during I/R injury. Thus, drugs, such as Repertaxin, developed to block the function of the CXCR2 receptor may be effective at preventing reperfusion injury in relevant clinical situations.
 ...
PMID:Repertaxin, a novel inhibitor of rat CXCR2 function, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury. 1530 76


<< Previous 1 2 3 4 5 6 Next >>