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)

Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A function in 40 patients with advanced cancer using the erythromycin breath test. Both the traditional C(20min) measure and the recently proposed 1/T(MAX) values were estimated. The marker of acute-phase response, C-reactive protein and the pro-inflammatory cytokines IL-6, IL-1beta, TNFalpha and IL-8 were measured in serum or plasma at baseline. Cancer patients with an acute phase response (C-reactive protein >10 mg x l(-1), n=26) had reduced metabolism as measured with the erythromycin breath test 1/T(MAX) (Kruskal-Wallis Anova, P=0.0062) as compared to controls (C-reactive protein < or =10 mg x l(-1), n=14) Indeed, metabolism was significantly associated with C-reactive protein over the whole concentration range of this acute-phase marker (r=-0.64, Spearman Rank Correlation, P<0.00001). C-reactive protein serum levels were significantly correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The reduction in cytochrome P450 3A function with acute-phase reaction was independent of the tumour type and C-reactive protein elevation was associated with poor performance status. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population.
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PMID:Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response. 1217 94

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite improvements in treatment, pulmonary disease still remains the primary cause of death among these patients. In order to introduce a normal CFTR gene copy into airway epithelial cells, adenoviral vectors (AV) have been developed. AV are known to induce an inflammatory reaction that limits transgene expression, and can be potentially harmful. No human study has clearly monitored simultaneously, systemic and local inflammatory reaction, during AV administration. We report here the levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) in plasma and bronchoalveolar lavage fluid (BALF) from six cystic fibrosis patients receiving AV encoding CFTR (AdCFTR). AdCFTR was administered to three cohorts of two patients into the nose on day 0, at doses ranging from 105 to 4 x 108 plaque-forming units (pfu), followed, on day 1, by aerosolization of 107 to 5.4 x 108 pfu. In order to ensure that patients were in the best clinical condition, and to further attenuate the broncho-pulmonary inflammation secondary to bacterial infection, they received antibiotic therapy, two weeks prior to AdCFTR administration, until 9 to 11 days after. We found that antibiotics markedly decreased CRP, TNF-alpha, IL-6, IL-1Ra levels in blood. In BALF, antibiotics slightly decreased TNF-alpha levels but had no effect on IL-8 and IL-1Ra, while IL-6 levels increased. AdCFTR administration did not induce any systemic or local cytokine release. In both blood and BALF, CRP, IL-8, IL-1Ra, TNF-alpha decreased, while IL-6 levels increased between day -7 and day 3. One patient presented an asymptomatic increase of all parameters in the BALF on day 7. Twenty one days later, he displayed a clinical deterioration suggestive of an exacerbation. In conclusion, this study demonstrates that antibiotic administration tends to attenuate systemic but not local broncho-pulmonary inflammation in CF patients. In the setting of our study, AdCFTR administration did not induce cytokine release. Further studies are necessary to investigate other inflammatory markers and the mechanisms involved during AV-mediated gene transfer for a better understanding of the immune reaction, which continues to hamper the development of gene therapy for CF patients.
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PMID:Cytokine pattern in cystic fibrosis patients during antibiotic therapy and gene therapy using adenoviral vector. 1223 76

We studied longitudinally inflammatory reactions and serum C-reactive protein (S-CRP) levels in 52 colorectal cancer patients treated with a median of six 3-weekly cycles of raltitrexed 1.5-3.0 mg m(-2) combined with oral carmofur (1-hexylcarbomoyl-5-fluorouracil) 300-400 mg m(-2) on cycle days 2-14. Thirty-nine (75%) of these patients had fever on days 2 to 9 after receiving raltitrexed, 49 (94%) had fatigue Gr. > or = 1, and 49 (94%) elevated S-CRP without a documented infection. The systemic inflammatory composite score (consists of body temperature, fatigue, S-CRP, interleukin-6 (S-IL-6), S-IL-8, and tumour necrosis factor-alpha (S-TNF alpha) levels) was calculated in a cross-sectional one-cycle study involving 60 colorectal cancer patients treated with single-agent raltitrexed, raltitrexed and carmofur, or 5-fluorouracil-based chemotherapy (n=20 in each group). The median S-CRP, S-IL-6, and S-TNF alpha levels were higher 7 days after giving raltitrexed (57 vs 23 mg l(-1), 64 vs 10 ng l(-1), and 11 vs 10 ng l(-1), respectively) or raltitrexed+carmofur (142 vs 10 mg l(-1), 64 vs 10 ng l(-1), and 16 vs 9 ng l(-1), respectively) than at baseline (P<0.01 for each comparison), but not when 5-fluorouracil-based regimens were administered. These findings suggest that colorectal cancer patients treated with raltitrexed may develop drug-related systemic inflammation, which may be difficult to discriminate from infection.
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PMID:Raltitrexed treatment promotes systemic inflammatory reaction in patients with colorectal carcinoma. 1223 67

The aim of this study was to investigate the effects of stent carbon coating on inflammatory response. The authors serially measured plasma concentrations of C-reactive protein (CRP), fibrinogen, and several cytokines (tumor necrosis factor, interleukin [IL]-1-beta, IL-6, and IL-8) in patients with single-vessel coronary stenosis who underwent primary stent implantation. None of the subjects had inflammatory or infectious disease at the time of the procedure. Forty-six patients (38 males; mean age 55 +/-9 years) were studied. Blood samples were collected before and at 2, 4, 6, 24, and 48 hours after stent implantation. Patients were randomly assigned 1 of 2 different stent types, an uncoated MAC (AMG Raesfeld-Erle, Germany) (UC-MAC) or a carbon-coated MAC (CC-MAC) stent. Implantations were performed without predilatation, and stents were deployed at a maximum pressure of 6 atmospheres for 90 seconds. Of the 46 patients, 14 had stable, 27 had unstable, and 5 had atypical angina. According to ACC/AHA classification, 35 lesions (76.1%) were type A, 10 (21.7%) were type B, and 1 (2.2%) was type C. Single stenosis of 28 left anterior descending, 12 circumflex, and 6 right coronary arteries were treated. Serum IL-6 increased in both the UC-MAC and CC-MAC groups, with concentrations significantly elevated above baseline at 6 hours, and then decreasing after 24 hours (baseline, 6-hour, and 24-hour values = 3.1 +/-2.3, 5.7 +/-3.8, and 6.3 +/-4.6 pg/mL, respectively, in UC-MAC; 3.7 +/-2.6, 6.2 +/-6.0, and 4.6 +/-3.7 pg/mL, respectively, in CC-MAC [p=0.002]). Plasma fibrinogen, CRP, and leukocyte concentrations also increased in both groups over the 24 hours (p < 0.05). The elevations of IL-6, CRP, and fibrinogen were similar in the 2 groups. The percent increases in IL-6, fibrinogen, and CRP were not associated with stent length, size, or clinical presentation (all p > 0.05). The results showed that stent implantation increases plasma IL-6, fibrinogen, and CRP concentrations, but carbon coating of the stent does not seem to affect this inflammatory response.
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PMID:Carbon coating of stents has no effect on inflammatory response to primary stent deployment. 1236 64

Previous evidence has shown that coronary angioplasty leads to the release of inflammatory mediators. In this study, we sought to characterize the systemic inflammatory response after coronary stent implantation in patients with unstable angina by measuring different protein markers. Peripheral blood samples were taken before and 24 h, 48 h, and 7 days after successful coronary stenting in 58 patients. Several markers of acute-phase response were determined: C-reactive protein (CRP), alpha2-macroglobulin, haptoglobin, acid alpha1-glycoprotein, prealbumin and albumin. Besides, proinflammatory cytokines (tumor necrosis factor-alpha, IL-6, IL-8) and the anti-inflammatory cytokine IL-10 were also measured. We have found that coronary angioplasty with stent implantation produces a systemic inflammatory response with a rise in inflammation markers concentration. CRP plasma levels declined 1 week after the intervention, but the other marker levels were even higher after 7 days. IL-6 was the only cytokine whose plasma levels significantly increased in peripheral blood after stenting, with a rise after 24 h, maintained after 48 h, and decreased to near-basal levels after 1 week. There was a good correlation between CRP and IL-6 plasma levels (r=0.5, p<0.001). IL-10 levels were slightly decreased after 24 h. Although no significant differences in the means at different time points were found, there was a decrease in IL-10 in most patients 24 h after the intervention. These results indicate that coronary stent implantation induces a systemic inflammatory reaction, with a temporal increase in the concentration of the inflammation markers, especially CRP and IL-6. Since these markers had been previously used as prognostic markers, this needs to be taken into account in patients undergoing stent implantation.
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PMID:Inflammatory response to coronary stent implantation in patients with unstable angina. 1239 2

A new respiratory virus, human metapneumovirus, was recently identified. We detected this virus by PCR in ten (8%) of 132 consecutive children admitted to Turku Hospital, Finland, for acute expiratory wheezing (median age 7 months, range 4-25). The mean duration of hospital stay was 2.5 days (SD 1.6) and mean duration of respiratory symptoms was 19 days (8). The white blood cell count, C-reactive protein, and regulated upon activation, normal T-cell-expressed and T-cell-secreted (RANTES) concentrations in nasal secretion remained low, whereas interleukin 8 concentrations in nasal secretion were high. Human metapneumovirus is a clinically important causative agent of acute wheezing in young children.
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PMID:Metapneumovirus and acute wheezing in children. 1242 87

Histologic results of the placenta are usually not available within the first days of life. We identified inflammatory variables in tracheal aspirates and blood that were associated with histologic chorioamnionitis (HC). A derivation cohort consisted of 62 neonates and a validation cohort of 57 neonates with a gestational age < 31 wk and ventilated on d 1. Tracheal aspirates were taken on d 1 and on d 3, if the patient was still ventilated. HC was diagnosed by light microscopy. Logistic regression was used to identify independent factors in the derivation cohort associated with HC at d 1, 2, and 3. Model performance was studied using receiver operating characteristic curve analysis. Independent factors associated with HC were, at d 1, tracheal aspirate IL-8 >or= 917 pg/mL (odds ratio, 60.7; 95% confidence interval, 11-328); at d 2, blood C-reactive protein >or= 14 mg/L (odds ratio, 9.2; 95% confidence interval, 2-38), blood white blood cell count >or= 10400/mm3 (odds ratio, 7.4; 95% confidence interval, 2-28); and at d 3, blood neutrophil count >or= 4968/mm3 (odds ratio, 14; 95% confidence interval, 3-57). The association with HC was less at d 3 (area under receiver operating characteristic curve, 0.77) when compared with the d 1 model (area under the curve, 0.88; p = 0.09). The models performed equally well in the validation cohort (goodness-of-fit test, p > 0.05). We conclude that the d 1 and d 2 models can be used as diagnostic factors for HC. Tracheal aspirate IL-8 taken immediately after birth was equally accurate in the diagnosis of HC as systemic inflammatory response at d 2 and better than on d 3.
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PMID:Relationship between histologic chorioamnionitis and early inflammatory variables in blood, tracheal aspirates, and endotracheal colonization in preterm infants. 1267 4

C-reactive protein (CRP) and serum amyloid P component (SAP) are acute phase proteins, whose concentrations increase within 24 h of inflammation along with concentration of IL-8. Polymorphonuclear neutrophil leukocytes (PMNs) form the earliest barrier protecting an injured organ during acute phase response. The aim of present work was to study interactions between CRP, SAP and IL-8, and to estimate the role of these interactions in regulation of neutrophil transendothelial migration. The results have shown that IL-8 binds to immobilized but not to free CRP. Binding of IL-8 to immobilized SAP was less strong. SAP like IL-8 increased CD11/CD18 integrin expression. IL-8 did not abolish the effect of SAP, and the mixture of IL-8 and SAP has stimulated CD11/CD18 expression. CRP upregulated CD18 but not CD11b expression. Under simultaneous action of CRP and IL-8, the stimulatory effect on CD11b and CD18 was abolished. The expression of fibronectin receptor was reduced by either IL-8 or CRP but increased by SAP. Effect of each protein was downregulated after following preincubations: CRP+SAP, CRP+IL-8 or SAP+IL-8. The mixtures of CRP with SAP, CRP with IL-8 or SAP with IL-8 showed no chemotactic activity, although each of the proteins was chemoattractive. Thus, acute phase proteins and IL-8 can act as anti-inflammatory factors upon binding each other. In summary, CRP and SAP influence PMN adhesion, migration and expression of CD11b/CD18 and fibronectin receptors, and can modulate the action of IL-8 on PMN attachment to endothelium and fibronectin, and on PMN traffic through the extracellular matrix during transendothelial migration.
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PMID:Interactions of C-Reactive Protein and Serum Amyloid P Component with Interleukin-8 and Their Role in Regulation of Neutrophil Functions. 1268 91

Information regarding the inflammatory response in African tick-bite fever (ATBF), an emerging spotted-fever-group rickettsiosis, in international travelers to sub-Saharan Africa, is scarce. Plasma/serum levels of von Willebrand factor (vWF), soluble (s) E-selectin, tumor necrosis factor-alpha, interleukin (IL)-6, interferon-gamma, IL-10, IL-13, IL-8, RANTES, macrophage inflammatory protein-1alpha, and C-reactive protein were studied, at both first presentation and follow-up, in 15 patients with travel-associated ATBF and in 14 healthy travelers who served as control subjects. Our main and novel findings are the following: (1) patients with ATBF had increased levels of vWF and sE-selectin, with a subsequent decrease at follow-up; (2) with the exception of IFN-gamma, levels of cytokines and chemokines were also increased in these patients at the first presentation; and (3) IL-10 and IL-13 tended to increase during follow-up, whereas most of the inflammatory cytokines decreased. The induction of these mediators and the balance between them may be critical both for the regulation of inflammation and for protective immunity in ATBF.
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PMID:Systemic inflammatory responses in African tick-bite fever. 1269 16

To date, there has been little research examining how elevated ambient temperatures exert an additional effect on the acute immune response to endurance exercise. Seven endurance-trained, non-heat-acclimated men [mean (95% confidence interval): 29.7 (25.9-33.5) years, .VO(2max) 66.3 (61.3-71.3) ml.kg(-1).min(-1)] performed two 60-min treadmill runs (75% .VO(2max)) in two different environments (EX1: 18 degrees C/50% room temperature/relative humidity and EX2: 28 degrees C/50% room temperature/relative humidity) with a 7-day interval between the runs. Blood samples were drawn at rest and 0, 0.5, 3, 24, and 48 h after exercise. Compared to EX1, exercise-induced increases in core temperature, sweating rate, heart rate, plasma norepinephrine, cortisol, human growth hormone, and neutrophil and monocyte counts were significantly (5% level) more pronounced after EX2. In contrast, responses of plasma epinephrine, myeloperoxidase, interleukin (IL)-6 as well as lymphocyte counts were similar in EX1 and EX2. Plasma concentrations of IL-8 and C-reactive protein were affected by neither exercise nor by additional heat exposure. Our results suggest that the additional impact of elevated ambient temperatures on stress responses to endurance exercise in trained subjects seems to affect primarily the cardiocirculatory and hormonal systems, and resulting changes in neutrophil and monocyte cell-trafficking. In contrast, heat stress does not seem to exert large additional effects on the acute immune response to endurance exercise as performed in the present study.
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PMID:Impact of elevated ambient temperatures on the acute immune response to intensive endurance exercise. 1273 44


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