Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, which is relatively insensitive to inhaled corticosteroids. The extent of the pulmonary inflammation in COPD correlates with disease severity, and it is thought to play a significant role in disease progression. We have evaluated a selective p38alpha-selective mitogen-activated protein kinase (MAPK) inhibitor, indole-5-carboxamide (ATP-competitive inhibitor of p38 kinase) (SD-282), in an 11-day model of tobacco smoke (TS)-induced pulmonary inflammation in A/J mice, by using dexamethasone as a reference steroid. Two oral treatment paradigms were evaluated in this TS model: prophylactic with daily pretreatment before each daily exposure, and therapeutic with daily treatment for 6 days commencing after 5 days of smoke exposure. Bronchoalveolar lavage and histological evaluation of lung sections taken after exposure to TS revealed an inflammatory response composed of increased numbers of macrophages and neutrophils and enhanced mucin staining. Phospho-p38 staining in macrophages and type II epithelial cells after TS exposure was also observed. Given prophylactically or therapeutically, dexamethasone failed to inhibit any of the TS-induced inflammatory changes. By contrast, SD-282 inhibited TS-induced increases in macrophages and neutrophils. Furthermore, SD 282 reduced TS-induced increases in cyclooxygenase-2 and interleukin-6 levels, and phospho-p38 expression in the lungs. In conclusion, SD-282 markedly reduced TS-induced inflammatory responses when given prophylactically or therapeutically whereas dexamethasone was ineffective. This is the first evidence that a p38alpha-selective MAPK inhibitor can exert pulmonary anti-inflammatory activity in a TS exposure model when given in a therapeutic mode, establishing the potential of p38 MAPK inhibitors as a therapy for COPD.
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PMID:p38alpha-selective mitogen-activated protein kinase inhibitor SD-282 reduces inflammation in a subchronic model of tobacco smoke-induced airway inflammation. 1805 68

The aim of the present study was to assess circulating levels of VEGF (vascular endothelial growth factor), a biomarker with prognostic significance in cardiovascular disease, and markers of systemic inflammation in patients with stable and exacerbated COPD (chronic obstructive pulmonary disease). Lung function parameters, arterial blood gas analysis and circulating levels of VEGF, IL-6 (interleukin-6), TNF-alpha (tumour necrosis factor-alpha), CRP (C-reactive protein), fibrinogen and the peripheral blood neutrophil cell count were assessed in 30 patients on admission to the hospital for acute exacerbation of COPD, in 30 age-, gender- and BMI (body mass index)-matched patients with stable COPD, and 30 matched controls with normal lung function. Patients with acute exacerbated COPD had higher circulating concentrations of VEGF (P<0.001), IL-6 (P<0.05) and CRP (P<0.01) and an increased blood neutrophil cell count (P<0.05) compared with patients with stable COPD and healthy controls. VEGF levels in exacerbated COPD correlated with systemic inflammatory markers, such as CRP (r=0.61, P<0.005), IL-6 (r=0.46; P<0.01) and fibrinogen (r=0.39, P<0.05). In patients with stable COPD, there was a significant relationship between circulating VEGF levels and the percentage of the predicted FEV(1) (forced expiratory volume in 1 s) (r=0.47, P<0.01). Recovery from the exacerbation resulted in a significant decrease in both circulating VEGF levels and markers of systemic inflammation. In conclusion, circulating levels of VEGF and markers of systemic inflammation are up-regulated in patients with acute exacerbated COPD and decrease after recovery from the exacerbation.
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PMID:Circulating vascular endothelial growth factor and systemic inflammatory markers in patients with stable and exacerbated chronic obstructive pulmonary disease. 1830 13

While recent studies have shown that patients with COPD and patients with asthma exhibit evidence of airway and systemic inflammation, markers of systemic inflammation have not been compared between the two diseases. To evaluate circulating inflammatory markers, blood was sampled from 111 patients with COPD, 75 control subjects and 46 asthmatic patients (some of whom were smokers). Measurements of WCC, serum levels of fibrinogen, high-sensitivity c-reactive protein (hs-CRP), interleukin-8 (IL-8), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor (TGF)-beta1, tissue inhibitors of metalloproteinase (TIMP)-1, neutrophil elastase and alphal-antitrypsin (alpha1-AT) were done. Serum TNF-alpha, IL-6, and TIMP-1 concentrations were significantly higher in patients with stable COPD and patients with asthma than in control patients. Serum alpha1-AT levels were significantly higher in COPD patients than in asthmatic patients and control subjects and serum TGF-beta1 levels were higher in asthma patients than in COPD patients. Smoking status had no effect on markers in COPD and asthmatic patients. Although COPD and asthma share common markers of systemic inflammation, serum levels of TGF-beta1 and alpha1-AT may reflect differences between the diseases.
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PMID:[Systemic inflammation in COPD and asthma: similarities and differences]. 1859 88

Interleukin-6 (IL-6) is a potential mediator of systemic effects of Chronic Obstructive Pulmonary Disease (COPD). In the present case-control study we investigated the association of promoter polymorphisms of this gene and COPD in a cohort of 191 patients, smokers without COPD (n=75) and a healthy control population (n=296). Besides spirometry, exercise capacity (6MWD, 6 min walking distance) and body mass index (BMI) were measured in COPD patients. Genotyping of the IL-6 polymorphisms at positions -174, -572 and -597 was performed. The -597G/A and -174G/C polymorphisms were not associated with the disease. However, the -572G/C polymorphism was significantly associated with COPD susceptibility under a dominant model of inheritance. The frequency of the genotypes containing the C allele was significantly lower in the COPD cases (9.9%) compared with the healthy control group (16.9%) and smokers (23.1%), (OR=0.46, p=0.032 and OR=0.28, p=0.012, respectively). The GCG (-597/-572/-174) haplotype was significantly associated with the disease (OR=0.37, p=0.022, COPD cases vs. healthy subjects and OR=0.17, p=0.011, COPD cases vs. smokers). Moreover, a borderline association was also found for the -572G allele and hypoxemia (PaO(2)<60 mmHg) (p=0.05). Our data suggest that the IL-6 -572C allele may confer a diminished risk of developing COPD.
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PMID:Association of IL-6 gene polymorphisms and COPD in a Spanish population. 1869 4

Apart from the deleterious effects on the lungs, chronic obstructive pulmonary disease (COPD) should be considered a complex, systemic disease involving several organs and systems. The nature and course of systemic inflammation in COPD is important since there is a potential for anti-inflammatory therapy. The objective of the current study was to assess biomarkers of systemic inflammation in stable and exacerbation phases of COPD patients as compared to healthy controls. We also investigated the course of these biomarkers after COPD exacerbation to evaluate their usefulness for disease monitoring. Eighty-three stable patients with moderate to very severe COPD, 20 patients in exacerbation phase, and 30 subjects with normal pulmonary function were included. Serum tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) levels were measured once in stable COPD patients and controls and three times in the COPD exacerbation group during follow-up. TNF-alpha and IL-6 levels were higher than in controls in both stable and exacerbation groups. Although NO was not higher in the stable COPD group than in controls, it was higher in the exacerbation group. In follow-up after the exacerbation period, significant alteration was not detected in cytokine or NO levels compared to admission. Raised serum levels of TNF-alpha and IL-6 support their use as biomarkers of the systemic inflammatory response in stable COPD patients. However, the circulating biomarkers we have studied are not found to be useful either as indicators of COPD exacerbation or for monitoring recovery after exacerbation.
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PMID:Biomarkers of systemic inflammation in stable and exacerbation phases of COPD. 1880 87

Ghrelin is an important orexigenic hormone that reduces fat oxidation and increases adiposity. This study investigated plasma ghrelin levels in Chinese Uygur patients with chronic obstructive pulmonary disease (COPD). Plasma ghrelin and anabolic and catabolic factors were measured in 38 patients and 24 control subjects. COPD patients were divided into two groups based on body mass index (BMI): underweight (BMI < 20 kg/m(2), n = 18) or normoweight (BMI > or = 20 kg/m(2), n = 20). Plasma ghrelin levels were found to be significantly higher in underweight than in normoweight patients or healthy controls. Circulating tumour necrosis factor-alpha and interleukin-6 concentrations were significantly higher in underweight than in normoweight patients, whereas insulin concentrations were significantly lower. Plasma ghrelin levels correlated negatively with forced expiratory volume in 1 s (FEV(1); r = 0.35), but did not significantly correlate with FEV(1)/forced vital capacity. Plasma ghrelin levels were elevated in underweight COPD patients and were associated with cachexia and abnormal pulmonary function.
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PMID:Plasma ghrelin levels and weight loss in Chinese Uygur patients with chronic obstructive pulmonary disease. 1909 48

The pathways underlying chronic obstructive pulmonary disease exacerbations (ECOPD) remain unclear. This study describes the clinical, functional and biochemical changes during recovery from ECOPD. Thirty hospitalized patients with Anthonisen's type-I ECOPD were evaluated on days 0 (admission), 3, 10 and 40. A five-symptom score (TSS), performance status and quality of life were evaluated. Post-bronchodilator spirometry, blood gases, oxidative stress, C-reactive protein (CRP), serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and fibrinogen were also measured. Patients were classified as early- or late-recoverers, based on whether dyspnea had returned to pre-exacerbation level by day 10. Most clinical, functional and biochemical parameters improved during follow-up. CRP and IL-6 levels reduced on Day 3 (p<0.05), whereas SAA on Day 10 (p<0.01). TNF-alpha was reduced on Days 3 and 10, but on Day 40 its levels returned to baseline. Fibrinogen and WBC reduced only by day 40. TSS and dyspnea were correlated inversely with FEV(1) on days 3, 10 and 40. Although late-recoverers had lower FEV(1) on admission, none of the reported measurements on admission and day 3 predicted early recovery. During recovery from ECOPD, symptomatic improvement correlates only with post-bronchodilator FEV(1) whereas systemic inflammatory burden subsidence does not correlate with clinical and functional changes. Although late-recoverers have lower FEV(1) on admission, none of the measured parameters is able to predict early symptomatic recovery.
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PMID:Clinical, functional and biochemical changes during recovery from COPD exacerbations. 1912 27

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death. Although the underlying pathomechanism remains poorly understood, COPD is accompanied by increased cellular stress and inflammation. We investigated serum contents of heat shock proteins (HSP 27, 60, 70, 90 alpha), 20S proteasomes, C-reactive protein (CRP), and interleukin-6 (IL-6) in patients with mild or severe COPD, healthy smokers and nonsmokers. HSP27, HSP70 and HSP90 alpha were significantly altered in patients suffering from COPD as compared to controls. HSP27 and HSP70 are potential novel serum markers for the diagnosis of COPD in the smoking population. This is the first study to demonstrate elevated serum levels of the described heat shock proteins in patients with COPD. We showed sensitivity and specificity of serum HSP27 and HSP70 as diagnostic markers for COPD.
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PMID:Elevated HSP27, HSP70 and HSP90 alpha in chronic obstructive pulmonary disease: markers for immune activation and tissue destruction. 1935 Aug 47

People with chronic obstructive pulmonary disease (COPD) suffer from muscle dysfunction which seems to be partly caused by systemic inflammation. Muscle protein breakdown as well as synthesis might be affected by this systemic inflammation. Additionally, it seems to induce excessive oxidative stress and reduce the level of growth-stimulating factors. As exercise training can have an anti-inflammatory effect in healthy people, the main question in this review is whether exercise (training) can also induce such effects in patients with COPD. However, because of the known inflammatory response after an acute bout of exercise, some researchers are afraid that exercise might actually worsen the inflammation in COPD. Recent evidence suggests, however, that the response might actually be anti-inflammatory and thus beneficial. Unfortunately, the evidence about the response of the inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 to exercise in patients with COPD is inconsistent, making it impossible to conclude whether a single exercise bout is harmful or beneficial in patients with COPD. Long-term exercise training in healthy people as well as in patients with chronic heart failure, another chronic inflammatory disease, seems to have beneficial effects on the inflammatory response. In patients with COPD, however, no training-induced changes in cytokine levels have been found and it must be concluded that physical exercise training does not seem to have an anti-inflammatory effect in COPD. On the other hand, it does not have a proinflammatory effect, and since patients with COPD benefit from exercise training with regard to other health parameters it is still recommended that they exercise regularly.
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PMID:The potential anti-inflammatory effect of exercise in chronic obstructive pulmonary disease. 1967 44

Chronic obstructive pulmonary disease (COPD) and lung cancer are two diseases that are related to smoking in humans. The molecular mechanism linking these two diseases is poorly understood. Matrix metalloproteinase 12 (MMP12) is a member of the MMP family, which can be induced by smoking. Because MMP12 overexpression in epithelial cells has been reported in inflammation-triggered lung remodeling, a murine CCSP-rtTA/(tetO)(7)-MMP12 bitransgenic model was created. In this model, MMP12-Flag fusion protein overexpression and its increased enzymatic activity were observed in the lung in an inducible manner, which led to inflammatory cell infiltration and increased epithelial growth. In sequential events, spontaneous emphysema and bronchioalveolar adenocarcinoma were developed as a result of MMP12 overexpression. During this process, the concentration of interleukin-6 was steadily increased in bronchioalveolar lavage fluid, which activated the oncogenic signal transducer and activator of transcription 3 (Stat3) in alveolar type II epithelial cells. Expression of Stat3 downstream genes that are known to stimulate inflammation and tumor formation was significantly increased in the lung. When tested in humans, MMP12 up-regulation was highly associated with COPD and lung cancer in patients. Together, these studies support that MMP12 is a potent proinflammatory and oncogenic molecule. MMP12 up-regulation plays a critical role in emphysema to lung cancer transition that is facilitated by inflammation.
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PMID:Matrix metalloproteinase 12 overexpression in lung epithelial cells plays a key role in emphysema to lung bronchioalveolar adenocarcinoma transition. 1970 65


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