Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients.

Godoy, Irma; Donahoe, Michael P.; Calhoun, William J.; Mancino, Juliet; Rogers, Robert M.

doi:10.1164/ajrccm.153.2.8564110

Cited by 298 publications

(189 citation statements)

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“…It is line with studies showing relationship between losing weight and serum TNF-α in COPD [8,12,15,37]. Alteration of FEV1 values might not be strictly related to change in airway calibre but may also depend on pulmonary elastolysis and reduced respiratory skeletal muscle forces, both processes likely to be influenced by TNF-α [6,15].…”

Section: Discussionsupporting

confidence: 85%

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

Moermans¹,

Heinen

Nguyen

et al. 2011

Cytokine

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Background: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease caused by repeated exposure to noxious gases or particles. It is now recognized that the disease also features systemic inflammation. The purpose of our study was to compare airway and systemic inflammation in COPD to that seen in healthy subjects and to relate the inflammation with the disease severity. Methods: Ninety-five COPD patients, encompassing the whole severity spectrum of the disease, were recruited from our outpatient clinic and rehabilitation center and compared to 33 healthy subjects. Induced sputum and blood samples were obtained for measurement of inflammatory cell count. Interleukin (IL)-4, IL-6, IL-10, TNF-α and IFN-γ produced by 24 h sputum and blood cell cultures were measured. Results: Compared to healthy subjects, COPD exhibited a prominent airway neutrophilic inflammation associated with a marked IL-10, IL-6 and TNF-α release deficiency that contrasted with a raised IFN-γ production. Neutrophilic inflammation was also prominent at blood level together with raised production of IFN-γ, IL-10 and TNF-α. Furthermore, sputum neutrophilia correlated with disease severity assessed by GOLD stages. Likewise the extent of TNF-α release from blood cells also positively correlated with the disease severity but negatively with that of sputum cell culture. Blood release of TNF-α and IL-6 negatively correlated with body mass index. Altogether, our results showed a significant relationship between cellular marker in blood and sputum but poor relationship between local and systemic release of cytokines. Conclusions: COPD is characterized by prominent neutrophilic inflammation and raised IFN-γ production at both bronchial and systemic level. Overproduction of TNF-α at systemic level correlates with disease severity and inversely with body mass index.

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Section: Discussionsupporting

confidence: 85%

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

Moermans¹,

Heinen

Nguyen

et al. 2011

Cytokine

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“…Stimulation of the bone marrow by cigarette smoke is probably mediated by soluble factors released from the lung. Alveolar macrophages are an important source of pro-inflammatory soluble factors and when stimulated by cigarette smoke produce factors such as TNF-a, IL-1, IL-8 and GM-CSF [13,14]. These factors are capable of stimulating haematopoietic precursors in the marrow and cause the release of granulocytes from the bone marrow into the circulation [46,47].…”

Section: Discussionmentioning

confidence: 99%

“…In previously reported animal studies, it was found that cigarette smoke exposure accelerated the release of PMNLs from the bone marrow, which was postulated to be mediated by soluble factors released from the lung [12]. Alveolar macrophages are an important source of pro-inflammatory mediators and, when stimulated by cigarette smoke, produce factors such as tumour necrosis factor-a (TNF-a), interleukin (IL)-1, IL-6, IL-8 and haematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) [13,14]. When these factors circulate they are capable of stimulating haematopoietic precursors resulting in accelerated proliferation and release of PMNLs from the bone marrow into the circulation [15,16].…”

mentioning

confidence: 99%

The response of human bone marrow to chronic cigarette smoking

Eeden¹,

Hogg²

2000

Eur Respir J

140

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Chronic cigarette smoking in humans causes leukocytosis. Animal studies show that chronic smoking shortens the transit time of polymorphonuclear leukocytes (PMNLs) through the bone marrow. The present study examines the response of human bone marrow to chronic cigarette smoking.Three characteristics of peripheral blood PMNLs that indicate active bone marrow release (band cell counts, surface L-selectin expression and myeloperoxidase (MPO) content), were measured in 38 healthy chronic smokers (23 5 pack-yrs) and 15 ageand sex-matched nonsmoking controls.The total white cell (6.8 0.3310 9 versus 5.3 0.2310 9 cells . L -1 , p<0.0001) and PMNL (4.2 0.18310 9 versus 3.2 0.1310 9 cells . L -1 , p<0.003) counts were higher in smokers as were the percentage (4.8 0.6 versus 1.1 0.2, p<0.0001) and total number (0.21 0.04310 9 versus 0.03 0.001310 9 cells . L -1 , p<0.01) of band cells. Flow cytometry showed that the mean fluorescence intensity (MFI) of L-selectin (3.2 0.2 versus 2.6 0.1, p<0.05) on PMNLs was higher in smokers. There was no difference in the baseline or N-formyl-methionyl-leucyl-phenylalanine-stimulated expression of CD63 or CD18/CD11b (surface markers of PMNL activation) between smokers and controls. The MPO content of PMNLs was higher in smokers (3.4 0.3 versus 1.7 0.2 MFI, p<0.05). Smokers with a low (<75% of the predicted value) diffusing capacity of the lung for carbon monoxide had higher PMNL MPO levels than smokers with a diffusing capacity of >75% pred (p<0.05).In conclusion, chronic smoking causes phenotypic changes in circulating polymorphonuclear leukocytes that are characteristic of chronic stimulation of the bone marrow and it is speculated that the increased number of immature polymorphonuclear leukocytes contributes to the chronic lung inflammation associated with cigarette smoking. Eur Respir J 2000; 15: 915±921.

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“…Tumour necrosis factor-a Plasma tumour necrosis factor (TNF)-a and its soluble receptor are increased in COPD patients [13][14][15], and TNF-a is also released from circulating cells in COPD patients with cachexia [16]. Circulating TNF-a appears to be related, at least in part, to hypoxaemia [14].…”

Section: Interleukin-6mentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,440

1,087

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Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

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Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients.

Cited by 298 publications

References 0 publications

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

Local and systemic cellular inflammation and cytokine release in chronic obstructive pulmonary disease

The response of human bone marrow to chronic cigarette smoking

Systemic manifestations and comorbidities of COPD

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