Systemic inflammation in COPD and asthma: similarities and differences]

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.     

Kinetics of serum cytokines reflect changes in the severity of chronic hepatitis C presenting minimal fibrosis

Our aims were to measure the kinetics of serum tumour necrosis alpha (TNF-α) and transforming growth factor beta (TGF-β) levels as markers of progression of disease in nontreated chronic hepatitis C virus (HCV)-infected patients with minimal or no fibrosis and minimal histology activity index (HAI) scores. Our study group consisted of 56 patients diagnosed with minimal (1) or no fibrosis (0) and minimal HAI (0–1) on their first biopsy as defined by Knodell and METAVIR scores. We compared their initial (entry of study) cytokine levels with a group of 103 HCV controls with minimal (0–1) to mild fibrosis (0–3) and mild HAI (5.5). Serum TNF-α and TGF-β levels were measured by enzyme-linked-immunosorbent-assay. A significant difference was seen in TNF-α levels at baseline in the study group vs. controls. Regardless of their HAI, there was a correlation between TGF-β and degree of fibrosis. As shown by their biopsies, during the 3 years (from entry to follow up), many of the patients that initially had minimal fibrosis progressed to higher degree of fibrosis. This progression is paralleled by an increase in TGF-β levels when comparing initial and follow-up levels. In conclusion, serum TNF-α reflects the progression of inflammation as seen in liver biopsies and TGF-β reflects the degree of fibrosis in HCV patients.     

Specific type IV phosphodiesterase inhibitor ameliorates thioacetamide-induced liver injury in rats

Background and Aims:  Rolipram is a specific type IV phosphodiesterase inhibitor that suppresses the activity of immune cells and the production of pro-inflammatory cytokines. In this study, we assessed the effect of rolipram on acute liver injury using thioacetamide (TAA)-induced liver injury in rats as a model.
Methods:  Rats were treated with rolipram (0.5–5 mg/kg, intraperitoneally) or vehicle and injected 30 min later with TAA (100 mg/kg, subcutaneously). Serum transaminase concentrations and tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) levels were measured and livers were examined for microscopic changes. Dose-dependent protection against TAA liver injury was based on transaminase levels and inflammatory cytokine production, and was measured 9 h after TAA when the peak release of cytokines occurred.
Result:  Rolipram suppressed liver injury based on serum aspartate transaminase (AST), alanine transaminase (ALT) and histology and reduced TNF-α, IL-1β and GRO/CINC-1 levels. Rolipram, at doses of 0.5–5 mg/kg, suppressed serum transaminase and TNF-α production in a dose-dependent manner, and these effects were significant at doses of 2.5 and 5 mg/kg.
Conclusion:  In our rodent model of acute liver injury, rolipram clearly reduced liver damage and inhibited pro-inflammatory cytokine production. These results suggest that specific type IV phosphodiesterase inhibitors, such as rolipram, have potent hepatoprotective effects that are associated with suppressing inflammatory cytokine production.     

Effects of probucol on hepatic tumor necrosis factor-α, interleukin-6 and adiponectin receptor-2 expression in diabetic rats

Background and Aims:  Probucol is a lipid-lowering agent with anti-oxidant effects. Oxidative stress and inflammation are important in the pathophysiology of insulin resistance. We aimed to evaluate the effects of probucol on liver histological changes, serum and hepatic levels of adipokines in rats with high fat-induced type 2 diabetes (T2D).
Methods:  Thirty-six rats were divided into a normal control group, a high fat-induced T2D group and a probucol treatment group. After six weeks of treatment with probucol, we evaluated liver histological changes and measured homeostasis model assessment index (HOMA-IR), serum superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin and hepatic TNF-α, IL-6 and adiponectin receptor-2 (adipoR2) mRNA.
Results:  The degree of hepatic steatosis and inflammation, HOMA-IR, serum ALT, TNF-α and IL-6 concentrations, and hepatic TNF-α and IL-6 mRNA expression in diabetic rats were significantly higher compared with normal controls. Serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression in diabetic rats were significantly lower compared with normal controls. Probucol significantly reduced the degree of hepatic steatosis, HOMA-IR, serum ALT, TNF-α and IL-6 concentrations, and hepatic TNF-α and IL-6 mRNA expression. Probucol significantly raised serum SOD and adiponectin concentrations and hepatic adipoR2 mRNA expression.
Conclusions:  In rats with high fat-induced T2D, treatment with probucol improved insulin sensitivity, hepatic steatosis by raising circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokines in the circulation and liver.     

Airway inflammation and anti-protease defences rapidly improve during treatment of an acute exacerbation of COPD

Background and objective:   There are few data on the short-term natural history of airway inflammation during severe episodes of acute exacerbation of COPD (AECOPD). An observational study was performed to determine how rapidly conventional treatment improves airway inflammation in patients admitted to hospital with AECOPD.
Methods:   Twenty-four consecutive patients with AECOPD were recruited and changes in sputum inflammatory indices were assessed after 2 and 4 days of treatment. The primary end-points included presence of bacteria and viruses, changes in sputum total cell counts (TCC) and polymorphonuclear leukocyte (PMN) differential counts, and levels of secretory leukocyte protease inhibitor (SLPI), IL-8 and TNF-α.
Results:   All patients received oral corticosteroids and 17 (71%) were also treated with oral antibiotics. A bacterial or viral pathogen was isolated from 12 patients (50%), and Aspergillus fumigatus was isolated from one. A positive bacterial culture was associated with increased sputum TCC and PMN count ( P  < 0.05), as well as higher levels of IL-8 and TNF-α ( P  < 0.05), and a trend towards lower sputum SLPI levels ( P  = 0.06). Sputum PMN numbers fell by 70% within the first 48 h of admission ( P  < 0.05), accompanied by an increase in sputum SLPI ( P  < 0.001) and reductions in the levels of TNF-α ( P  < 0.005) and IL-8 ( P  = 0.06), with no further significant change at 4 days.
Conclusions:   Conventional treatment for severe AECOPD is associated with rapid reduction of neutrophilic inflammation and improvement in anti-protease defences.     

Is portal hypertension associated with protein-losing enteropathy?

Background and Aim:  Hypoalbuminemia in patients with decompensated cirrhosis has traditionally been assumed to be a result of to impaired liver synthesis; however, protein-losing enteropathy (PLE) may also contribute. The aim of this study was to assess whether hypoalbuminemic cirrhotic patients with portal hypertension had evidence of PLE.
Methods:  Sixteen patients with alcoholic cirrhosis, hypoalbuminemia and portal hypertension underwent whole gut lavage with polyethylene glycol solution. The effluent obtained was analyzed for albumin, immunoglobulin (Ig)G and α1-antitrypsin (α1-AT). Serum C-reactive protein (CRP) was also measured to assess the systemic inflammatory response.
Results:  Twelve of the 16 enrolled patients had a persistently low albumin concentration at the time of lavage. Only one patient (who was subsequently found to have celiac disease) had elevated concentrations of lavage albumin, α1-AT and IgG levels. There was a significant correlation between lavage albumin and α1-AT ( r  = 0.671, P  = 0.024), and between lavage albumin and IgG ( r  = 0.614, P  = 0.045). There was no correlation between serum albumin and lavage proteins. Six patients had elevated serum CRP levels, but serum albumin or lavage protein concentrations did not correlate with serum CRP.
Conclusion:  There is no evidence of a significant PLE in patients with alcoholic cirrhosis, hypoalbuminemia and portal hypertension.     

Comparing the protective effects of ciprofloxacin, moxifloxacin and levofloxacin in mice with lipopolysaccharide-induced acute lung injuries

Background and objective:   Ciprofloxacin, moxifloxacin and levofloxacin are recognized immunomodulators. Their effects in acute lung injuries have not been tested. This study compared the immunoprotective effects of these agents in mice with lung injuries induced by LPS by measuring the cytokine profiles in the injured lung and the associated mortality.
Methods:   The development of lung injury and mortality was compared in mice pretreated with either ciprofloxacin, levofloxacin, moxifloxacin or saline (control group) after the intratracheal administration of LPS. BALF and serum were collected at 1, 3 and 6 h to measure the concentrations of tumour necrosis factor-α (TNF-α), IL-1β, IL-6, IL-10 and macrophage inflammatory protein-2 (MIP-2) using enzyme-linked immunoassay.
Results:   Levels of TNF-α, IL-1β and MIP-2 in the BAL of the ciprofloxacin group were significantly lower compared with those of controls (all P  < 0.0083) at 3 and 6 h after LPS challenge. There were no significant differences in the levels of these cytokines in the moxifloxacin and levofloxacin groups compared with controls. Overall, the 96-h survival for the mice pretreated with ciprofloxacin, but not for those pretreated with moxifloxacin or levofloxacin, was significantly greater than that of the control animals ( P  = 0.019).
Conclusions:   In the setting of LPS-induced lung injuries, ciprofloxacin appears to provide better anti-inflammatory properties and survival benefits than the other fluoroquinolones tested.     

Epithelial-mesenchymal transition induced by transforming growth factor-β1 in mouse tracheal epithelial cells

Background and objective:   Epithelial-mesenchymal transition (EMT) is the process by which differentiated epithelial cells undergo a phenotypic transition to mesenchymal cells. This process may occur in certain fibrotic diseases that involve airway remodelling. However, few studies have directly proved the occurrence of EMT in primary cultures of airway epithelial cells. The aim of this study was to clarify whether airway epithelial cells can differentiate into mesenchymal cells through EMT.
Methods:   Mouse tracheal epithelial cells (mTEC) were cultured in an air–liquid interface (ALI) culture system, in the presence or absence of transforming growth factor-β1 (TGF-β1). The expression of mesenchymal and epithelial cell markers was examined by immunofluorescence staining and western blotting. Secretion of matrix metalloproteinase (MMP)-9 into the culture medium was measured by ELISA. The phenotype of epithelial cells involved in EMT was also examined by immunofluorescence staining.
Results:   Immunofluorescence staining and western blotting revealed that TGF-β1 treatment for 14 days induced the expression of the mesenchymal markers, α-smooth muscle actin (α-SMA) and vimentin, and reduced the expression of the epithelial markers, zonula occludens-1 (Zo-1) and occludin. In addition, α-SMA and Zo-1 were colocalized within individual cells treated with TGF-β1. Concentrations of MMP-9 in the culture medium were significantly higher in TGF-β1-treated mTEC than in untreated cells. The basal cell markers, cytokeratin-5 and cytokeratin-17, were colocalized within the cells expressing α-SMA.
Conclusions:   EMT was induced by TGF-β1 in primary cultures of mTEC, suggesting that airway epithelial cells, possibly the basal cells, may be involved in airway remodelling through EMT.     

Evaluation of the anti-inflammatory effect of infliximab in a mouse model of acute asthma

Background and objective:   To evaluate the potential role of anti-tumour necrosis factor (TNF)-α mAb (infliximab) on the inflammatory response in a mouse model of acute asthma.
Methods:   BALB/c mice received intraperitoneal (i.p.) ovalbumin (OVA) on days 0 and 14, 100 μg of OVA intranasally on day 14 and 50 μg of OVA intranasally on days 25, 26 and 27. The low-dose (2.5 mg/kg) and high-dose (6.25 mg/kg) infliximab groups received i.p. infliximab before each i.p. sensitization and on challenge days 1, 6, 13, 20 and 27. The control group received i.p. injections of normal saline with alum on days 0 and 14 and normal saline without alum on days 14, 25, 26 and 27.
Results:   There were statistically significant decreases in the numbers of BAL fluid (BALF) neutrophils, eosinophils, as well as lung eosinophils in both the low- and high-dose infliximab groups when compared with the control OVA sensitized/challenged group. The lower dose of infliximab did not alter lung neutrophil counts, but a marked decrease was seen with the high dose of infliximab. After treatment with low and high doses of infliximab, BALF levels of regulated on activation normal T cell expressed and secreted (RANTES), granulocyte macrophage-colony stimulating factor (GM-CSF), TNF-α, IL-6, macrophage inflammatory protein (MIP)-2, and levels of RANTES, IL-4, GM-CSF, TNF-α, IL-6 and MIP-2 in lung tissue were significantly decreased when compared with the control OVA sensitized/challenged group. There was a significant decrease in BALF IL-4 only in the high-dose infliximab group.
Conclusions:   These results show that an anti-TNF-α mAb has a considerable anti-inflammatory effect on allergen-induced lung inflammation in an animal model of acute asthma.     

Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors

Aim:   Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F_2α during BMI lowering with orlistat (Xenical^®, Roche) or placebo.
Methods:   TNF-α, IL-6, and 8-epi PGF_2α evaluated in 376 subjects aged 18–75 years with BMI 28–38 kg/m² before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily.
Results:   Weight reduction was associated with decreasing (p < 0.001) levels of TNF-α and IL-6 in both orlistat and placebo groups. After 12 months, TNF-α was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-α correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF_2α correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001).
Conclusion:   Weight reduction was associated with decreasing levels of both TNF-α and IL-6. After 12 months of treatment, TNF-α levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.     

Hepatocyte steatosis in HCV patients promotes fibrosis by enhancing TGF-β liver expression

Aim:  The objective of this study was to examine the relationship between TGF-β expression in steatotic liver and the stage and yearly progression rate of fibrosis in chronic hepatitis C (CHC) patients.
Methods:  We examined 44 CHC fatty liver patients, using 76 non-steatotic CHC patients as controls. The stage of hepatic fibrosis was assessed on a score scale. TGF-β expression was determined with the use of monoclonal serum and the ABC three-step method.
Results:  We demonstrated a positive correlation of steatosis with the stage of fibrosis ( P  < 0.05). No relationship of thiskind was found with the yearly progression rate of fibrosis ( P  > 0.09). In steatotic biopsies, TGF-β expression index in portal spaces and lobules was found to be higher as compared to TGF-β expression in biopsies without steatosis ( P  < 0.05).
Conclusion:  In CHC patients steatosis induces the development of fibrosis by elevating the hepatic expression of TGF-β.     

Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains

Background and objective:   Infection with rhinovirus (RV) is the most common trigger for acute asthma and COPD. The aim of this study was to characterize the variability in the response of primary bronchial epithelial cells to infection with several strains of RV.
Methods:   RV strains, RV-43, RV-48 (major group RV), RV-47 (minor) and EV-68 (enterovirus), were cultured from subjects with acute asthma and compared with the laboratory RV strains, RV-16, RV-14 (major) and RV-1B (minor). Primary bronchial epithelial cells were obtained from healthy control and asthmatic subjects by endobronchial brushing. Response to infection was assessed by the release of IL-6, interferon (IFN)-γ induced protein (IP)-10 and IFN-β, as measured by ELISA. Viral replication was assessed by serial titration assays and cell viability by flow cytometry.
Results:   Major group RV strains and EV-68 all efficiently infected and replicated in epithelial cells causing little cell death. The clinical major group RV strains caused greater release of IL-6 and IP-10 compared with laboratory major group RV strains. Infection with minor group RV resulted in greater release of IP-10, IL-6 and IFN-β that was associated with induction of apoptosis and less efficient viral replication. Asthmatic bronchial epithelial cells were less able to respond by releasing IFN-β following infection with RV-1B.
Conclusions:   Considerable diversity exists in the response to RV strains, especially between minor and major group RV. The impaired IFN-β response in asthmatic bronchial epithelial cells may make them particularly susceptible to minor group RV.     

Ethanol alters production and secretion of estrogen-regulated growth factors that control prolactin-secreting tumors in the pituitary

Background:  Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol's mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine whether ethanol's lactotropic cell-proliferating action, like estradiol's, is associated with alteration in the production of 3 peptides that regulate cell growth: transforming growth factor beta 1 (TGF-β1), TGF-β3 and basic fibroblast growth factor (bFGF).
Methods:  Using ovariectomized Fischer-344 female rats, we determined ethanol's and estradiol's actions on lactotropic cell proliferation and growth-regulatory peptide production and release in the pituitary gland during tumorigenesis.
Results:  Ethanol increased basal and estradiol-enhanced mitosis of lactotropes in the pituitary glands of ovariectomized rats. The level of growth-inhibitory TGF-β1 was reduced in the pituitary following ethanol and/or estradiol treatment for 2 and 4 weeks. In contrast, ethanol and estradiol alone as well as together increased levels of growth-stimulatory TGF-β3 and bFGF in the pituitary at 2 and 4 weeks. In primary cultures of pituitary cells, both ethanol and estradiol reduced TGF-β1 release and increased TGF-β3 and bFGF release at 24 hours. Ethanol's effect on growth factor levels in the pituitary or growth factor release from the pituitary cells was less than that of estradiol. When ethanol and estradiol were applied together, their individual effects on these growth factors were amplified.
Conclusions:  These results confirm estradiol's modulation of pituitary growth factor production and release, and provide evidence that ethanol, like estradiol, alters the production and secretion of growth-regulatory peptides controlling lactotropic cell proliferation.     

The effects of warming methods on temperature, cardiac function and cytokines in plateletpheresis donors

Background and Objectives   Plateletpheresis is the most frequent type of apheresis, with demand for these products continuously increasing. Hypothermia is a common side-effect of apheresis, which may have an effect on the donor's body functions. The aim of this study was to examine the effects of warming methods on plateletpheresis donors' temperature, cardiac function and cytokines.
Materials and Methods   Fifty plateletpheresis donors were randomly assigned to a control group ( n  = 25) or a warming group ( n  = 25), with air and blood warmers during plateletpheresis. The effects of the treatment were examined by comparing body temperature, heart rate, blood pressure, Holter EKG pattern, serum interleukin-1β (IL-1β), interleukin-2 (IL-2), tumour necrosis factor-α (TNF-α) concentration, the white blood count, the white blood fraction, and the platelet count at a point in time between the two groups.
Results   In the control group, the tympanic temperature decreased more during apheresis compared to the warming group ( P  = 0·014). The decrease of diastolic blood pressure was significantly greater in the control group compared to the warming group ( P  = 0·010). As for cardiac function, the frequency of abnormal beats was generally higher in the control group, but the difference was not significant. IL-2 and TNF-α decreased significantly after plateletpheresis in the control group only, while there was no change in the warming group.
Conclusion   The decrease of temperature during plateletpheresis resulted in changes in haemodynamics and cytokines. The warming methods used in this study can prevent the decrease of temperature in donors, and may be helpful in maintaining the haemodynamic and cytokine balance.     

Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-β

Although many patients with chronic viral hepatitis C infection suffer from progressive liver disease, the rate of fibrosis progression is highly variable and some patients do not show any measurable progression. However, our ability to predict which patients progress is very limited. Since transforming growth factor-β (TGF-β) is a key mediator of liver fibrogenesis, we assessed the predictive role of TGF-β for fibrogenesis in chronic hepatitis C. We studied 39 patients with chronic hepatitis C in whom two liver biopsies were taken at least 12 months apart, and who did not receive therapy during this period. TGF-β was measured by bioassay and by ELISA in serum samples taken at the time of the first biopsies, and TGF-β was determined semiquantitatively by immunostaining of liver biopsy sections. Fibrosis was scored blinded in the biopsy samples by two pathologists independently. There was a close correlation between TGF-β serum levels and the rate of fibrosis progression. Patients with no progression of fibrosis had significantly lower (59 ng/mL ± 22) TGF-β serum levels than patients with progressive disease (115 ng/mL ± 20), and a TGF-β level below 75 ng/mL was predictive for stable disease. Immunohistology for TGF-β in biopsy samples was also predictive for progressive liver disease with fibrosis progression found in those patients displaying staining of hepatocytes and sinusoidal cells. No such correlation was found with other markers such as procollagen III peptide, viral load or transaminase levels. These results further support the role of TGF-β in liver fibrogenesis, and offer an opportunity to predict clinical disease progression, which may help in selecting patients who are in need of therapeutic interventions.     

Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats

Background and objective:   Epidemiological evidence indicates a close link between exposure to fungi and deterioration of asthma. However, the role of fungi as an exogenous precipitant for initiation and progression of asthma has been incompletely explored. In this study, the effects of Aspergillus fumigatus exposure on airway inflammation and remodelling in a rat model of chronic asthma were investigated.
Methods:   The rat model of chronic asthma was established by systemic sensitization and repeated challenge with ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. Changes in airway inflammation, remodelling and BHR were measured after exposure to the fungus.
Results:   Chronic inhalation of A. fumigatus spores elevated the production of T helper 2 (Th2) cytokines, increased the concentration of total serum IgE, and resulted in the recruitment of eosinophils and lymphocyte infiltration into the airways of asthmatic rats. Goblet cell hyperplasia, mucus hyperproduction and subepithelial collagen deposition were also induced by inhalation of the fungus. The remodelling changes induced by inhalation of the fungus paralleled the changes in BHR in this rat model of asthma.
Conclusions:   Chronic exposure to A. fumigatus aggravated Th2 airway inflammation, promoted airway remodelling and increased BHR in OVA-sensitized and -challenged rats.     

Peroxisome proliferator-activated receptor γ (PPAR) agonism reduces the insulin-stimulated increase in circulating interleukin-6 in GH replaced GH-deficient adults

Context  Peroxisome proliferator-activated receptor γ (PPARγ) agonists modify cardiovascular risk factors and inflammatory markers in patients with type 2 diabetes. GH treatment in GH-deficient (GHD) patients may cause insulin resistance and exerts ambiguous effects on inflammatory markers.
Objective  To investigate circulating markers of inflammation and endothelial function in GH replaced GHD patients before and after 12 weeks administration of either pioglitazone 30 mg/day ( N  = 10) or placebo ( N  = 10) in a randomized double-blind parallel design.
Methods  Circulating levels of interleukins (ILs)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, high sensitivity C-reactive protein, vascular cell adhesion molecule-I, and osteoprotegerin (OPG) were measured in the basal state and after a 2·5 h hyperinsulinaemic euglycaemic clamp.
Results  Insulin sensitivity improved in the group receiving PPARγ agonist ( P =  0·03). Serum IL-6 levels increased by 114 ± 31% (mean ± SE) in the entire group ( N  = 20) following the hyperinsulinaemic euglycaemic clamp ( P =  0·01) performed at study start. Twelve weeks of PPARγ agonist treatment significantly abrogated this insulin-stimulated increment in IL-6 levels compared to placebo ( P =  0·01). Furthermore PPARγ agonist treatment significantly lowered basal IL-4 levels ( P <  0·05).
Conclusions  (i) IL-6 levels increase during a hyperinsulinaemic clamp in GH replaced patients (ii) This increase in IL-6 is abrogated by PPARγ agonist treatment (iii) we hypothesize that PPARγ agonist-induced improvement of insulin sensitivity may obviate a compensatory rise in IL-6.     

Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma

BACKGROUND: Airway inflammation is associated with an increased expression and release of inflammatory reactants that regulate processes of cell migration, activation and degranulation. The purpose of this study was to quantify bronchial lavage (BAL) fluid and serum levels of chemokine (IL-8), secretory leukocyte protease inhibitor (SLPI), soluble intracellular adhesion molecules-1 (sICAM-1) and sCD14, as surrogate markers of inflammatory and immune response in asthma and chronic obstructive pulmonary disease (COPD) patients with similar disease duration time. METHODS: Biomarkers in serum and BAL fluid from asthma (n=13) and COPD (n=25) patients were measured using commercially available ELISA kits. RESULTS: We found that in asthma and COPD groups the concentrations of IL-8 and SLPI are significantly higher in BAL fluid than in serum, while levels of sICAM-1 and sCD14 in BAL fluid are significantly lower than in serum. Of these 4 measured biomarkers, only the BAL IL-8 was higher in COPD patients when compared to asthma (P<0.05). In both groups, BAL IL-8 correlated with SLPI (r=0.577, P<0.01 and r=0.589, P<0.05, respectively). In patients with COPD the BAL sICAM-1 correlated with sCD14 (r=0.576, P<0.01), while in asthma patients BAL sICAM-1 correlated with FEV(1)/FVC (r=0.418, P<0.01). Moreover, in asthma patients the serum SLPI correlated with sCD14 (r=0.688, P<0.01) and serum sICAM-1 negatively correlated with FEV(1)/FVC (r=-0.582, P<0.05). CONCLUSION: Our findings point to the importance of selecting a correct biological fluid when analyzing specific biomarkers, and also show that of 4 measured biomarkers, only the BAL IL-8 was higher in COPD patients when compared to asthma.