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      Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease

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          Abstract

          Background

          Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.

          Methods

          We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.

          Results

          Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001). A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001). Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).

          Conclusion

          Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.

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          Most cited references32

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          Airway eosinophilia in chronic bronchitis during exacerbations.

          To examine the nature and the degree of airway inflammation in chronic bronchitis during exacerbations, bronchial biopsies and sputum were obtained in 11 subjects with chronic bronchitis examined during an exacerbation, and in 12 subjects with chronic bronchitis examined under baseline conditions. All subjects were nonatopic. Lobar bronchial biopsies were assessed using histochemical and immunohistochemical techniques, and sputum was examined for differential cell counts of leukocytes. Subjects with bronchitis during exacerbations had, on average, 30-fold more eosinophils in their bronchial biopsies than did those examined under baseline conditions (p < 0.001). Although to a lesser extent, the numbers of neutrophils (p < 0.01), T-lymphocytes (CD3) (p < 0.05), VLA-1-positive cells (p < 0.01), and TNF-alpha positive cells (p < 0.05) were also increased during exacerbations. By contrast, the T-lymphocyte subpopulations (CD4 and CD8) and the numbers of macrophages, mast cells, IL-2R-positive cells, and IL-1 beta-positive cells were similar in the two groups of subjects, as well as the percentages of ICAM-1- and E-selectin-positive vessels. Eosinophils were also increased in sputum of subjects with exacerbations when compared with those examined under baseline conditions (p < 0.05). In conclusion, exacerbations of chronic bronchitis are associated with a marked airway eosinophilia and with a milder increase in the number of neutrophils, activated T-lymphocytes, and TNF-alpha-positive cells in the bronchial mucosa.
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            Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease.

            An increase in resting energy expenditure (REE) commonly occurs in patients with chronic obstructive pulmonary disease (COPD), the cause of which is as yet unknown. The objective of this study was to assess the relationship between REE, acute phase proteins, and inflammatory mediators in patients with COPD. Thirty patients were studied and 26 healthy age-matched subjects served as controls. REE was measured by indirect calorimetry and adjusted for fat-free mass (FFM) by bioelectrical impedance analysis. Tumour necrosis factor alpha (TNF-alpha), soluble tumour necrosis receptor (sTNF-R)55 and sTNF-R75, interleukin (IL)-6, IL-8, and lipopolysaccharide binding protein (LBP) were measured by ELISA. Fourteen patients had a normal REE and in 16 it was raised. The mean body mass index and fat mass were significantly lower in the latter but pulmonary function data were similar in the two groups. In the 30 patients with COPD the mean (SD) sTNF-R75 was 1.7 (1.0) ng/ml compared with 1.1 (0.4) ng/ml in the controls; C-reactive protein (CRP) was detectable (> 5 micrograms/ml) in eight patients compared with none of the control subjects, and LBP was 13.2 (7.7) micrograms/ml compared with 8.6 (3.1) micrograms/ml in the controls. The patients with a raised REE had increased mean levels of CRP compared with the patients with a normal REE (median 5.5 micrograms/ml (range 5-193) and < 5 micrograms/ml, respectively); the same was true for LBP (median 12.4 micrograms/ml (range 8.1-39.1) and 9.5 micrograms/ml (range 5.0-16.6), respectively), but sTNF-R55 and R75 and IL-8 were similar in the two groups. Of the 16 patients with a raised REE, the CRP level was increased in eight and normal in eight. In those with an increased level of CRP the FFM was decreased and LBP, IL-8, and sTNF-R55 and R75 were increased compared with those with normal CRP levels. A subset of patients with COPD with an increased REE and decreased FFM have increased levels of acute phase reactant proteins and inflammatory cytokines in their serum; these phenomena may be causally related.
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              Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease.

              Unexplained weight loss is common in chronic obstructive pulmonary disease (COPD). Blood levels of tumor necrosis factor-alpha (TNF-alpha), a cytokine causing cachexia in laboratory animals, are elevated in various human diseases associated with weight loss. We therefore prospectively measured TNF-alpha serum levels (immunoradiometric assay) in patients with clinically stable COPD (n = 30; all male; mean age, 65 yr) whose weight was less (Group I; n = 16) or more (Group II; n = 14) than the lower limit of normal taken from Metropolitan Life Insurance Company tables. The patients had no cause known to elevate TNF-alpha serum levels; notably, they were not infected. Group I patients had unintentionally lost weight during the previous year, whereas the weight of Group II patients had not changed during the same period. The two groups had similar chronic airflow obstruction and arterial blood gas impairment; hyperinflation and reduction in diffusing capacity were more pronounced in Group I, but differences were not significant. TNF-alpha serum levels (pg/ml; mean [SD]) were significantly higher in Group I than in Group II (70.2 [100.0] versus 6.7 [6.4]; p < 0.001). Group II TNF-alpha serum levels did not differ significantly from those of healthy subjects (7.8 [3.9]), whereas those of Group I were significantly higher (p < 0.001). Because renal function was in the normal range, we conclude that increased TNF-alpha production--and not decreased TNF-alpha clearance--is a likely cause of weight loss in patients with COPD.
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                Author and article information

                Journal
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central
                1471-2466
                2009
                5 April 2009
                : 9
                : 11
                Affiliations
                [1 ]Department of Respiratory and Critical Care Medicine, Sotiria Chest Hospital, Athens, Greece
                [2 ]Department of Microbiology, Immunology Laboratory, Sotiria Chest Hospital, Athens, Greece
                Article
                1471-2466-9-11
                10.1186/1471-2466-9-11
                2670813
                19344528
                cce0a257-db8f-4abf-8cc6-7270e87f74d7
                Copyright © 2009 Kythreotis et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 September 2008
                : 5 April 2009
                Categories
                Research Article

                Respiratory medicine
                Respiratory medicine

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