Differences in local versus systemic TNFα production in COPD: inhibitory effect of hyaluronan on LPS induced blood cell TNFα release

Dentener, M. A.; Louis, R.; Cloots, R. H. E.; Henket, M.; Wouters, E. F. M.
June 2006
Thorax;Jun2006, Vol. 61 Issue 6, p478
Academic Journal
Background: Chronic obstructive pulmonary disease (COPD) is characterised by both airway inflammation and systemic changes. To elucidate the relationship between local and systemic inflammation, tumour necrosis factor α (TNFα) production by sputum cells and blood cells of patients with COPD and controls was compared and the effect of the extracellular matrix compound hyaluronan (HA) on TNFα release was studied. Methods: Four study groups were included: 10 steroid free COPD patients, 8 steroid treated patients, 10 healthy smokers, and 11 healthy non-smokers. Sputum cells and blood were incubated for 24 hours with or without lipopolysaccharide (LPS) in the absence or presence of HA (122 kDa or HMW fragment). TNFα was measured by ELISA. Results: Sputum cells produced spontaneously high levels of TNFα but were unresponsive to LPS. Sputum cells from COPD patients (both steroid free and steroid treated) produced significantly less TNFα than cells from healthy non-smoking subjects (p=0.017 and p=0.001, respectively). In contrast, blood cells produced TNFα only in response to LPS. No differences were observed in TNFα production by blood cells between the patient groups and the control groups. HA (both fragments) partially blocked LPS (1 ng/ml) induced TNFα release by blood cells from all study groups, whereas TNFα production by sputum cells was not influenced by HA. Conclusion: These data indicate a difference between local and systemic TNFα production. Sputum cells of patients with COPD produced less TNFct than controls, which could contribute to impaired local defence. An inhibitory effect of HA on TNFα release in blood cells was observed which was similar in both patients and controls.


Related Articles

  • Role of TNFα in pulmonary pathophysiology. Mukhopadhyay, Srirupa; Hoidal, John R.; Mukherjee, Tapan K. // Respiratory Research;2006, Vol. 7, p125 

    Tumor necrosis factor alpha (TNFα) is the most widely studied pleiotropic cytokine of the TNF superfamily. In pathophysiological conditions, generation of TNFα at high levels leads to the development of inflammatory responses that are hallmarks of many diseases. Of the various pulmonary...

  • Elevated Plasma Hyaluronan Levels in Pulmonary Hypertension. Kalay, Nihat; Elcik, Deniz; Canatan, Halit; Kaya, Mehmet Gungor; Yarlioglues, Mikail; Oguzhan, Abdurrahman; Dweik, Raed A.; Aytekin, Metin // Tohoku Journal of Experimental Medicine;May2013, Vol. 230 Issue 1, p7 

    Pulmonary arterial hypertension (PAH) is a progressive disease, with a poor prognosis. The pathophysiologic mechanism of PAH is unknown, but may involve both tissue remodeling and inflammatory processes. Hyaluronan (HA) is a large glycosaminoglycan polymer and a major component of the...

  • Chilaiditi's sign. Saha, Kaushik // Journal of Advances in Internal Medicine;Jan-Jun2013, Vol. 2 Issue 1, p16 

    The article presents a case study of a 70-year-old man who was suffering from chronic obstructive pulmonary disease (COPD). He was investigated with hemogram blood test, electrocardiography and ultrasonography of abdomen. His chest X-ray poster anterior (PA) showed the signs of chilaiditi...

  • Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease. Xiaomin Dang; Xiaoyan Qu; Weijia Wang; Chongbing Liao; Ying Li; Xiaojin Zhang; Dan Xu; Baglole, Carolyn J.; Dong Shang; Ying Chang; Dang, Xiaomin; Qu, Xiaoyan; Wang, Weijia; Liao, Chongbing; Li, Ying; Zhang, Xiaojin; Xu, Dan; Shang, Dong; Chang, Ying // Respiratory Research;1/5/2017, Vol. 18, p1 

    Background: Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils. Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs)...

  • Smoking status and tumour necrosis factor-alpha mediated systemic inflammation in COPD patients. Tanni, Suzana E.; Pelegrino, Nilva R. G.; Angeleli, Aparecida Y. O.; Correa, Camila; Godoy, Irma // Journal of Inflammation;2010, Vol. 7, p29 

    Background: Smoking cause airway and systemic inflammation and COPD patients present low grade inflammation in peripheral blood. However, data on the influence of smoking itself on systemic inflammation in COPD patients are scarce. This study investigated the association between inflammation,...

  • CD46 Protects against Chronic Obstructive Pulmonary Disease. Grumelli, Sandra; Bao Lu; Peterson, Leif; Maeno, Toshitaka; Gerard, Craig // PLoS ONE;2011, Vol. 6 Issue 5, p1 

    Background: Chronic obstructive pulmonary disease and emphysema develops in 15% of ex-smokers despite sustained quitting, while 10% are free of emphysema or severe lung obstruction. The cause of the incapacity of the immune system to clear the inflammation in the first group remains unclear....

  • Association of Serum Magnesium Levels with Frequency of Acute Exacerbations in Chronic Obstructive Pulmonary Disease: A Prospective Study. Gumus, Aziz; Haziroglu, Muge; Gunes, Yilmaz // Pulmonary Medicine;2014, p1 

    Background. The course of chronic obstructive pulmonary disease (COPD) is accompanied by acute exacerbations. The purpose of this study is to determine the association of serum magnesium level with acute exacerbations in COPD (COPD-AE). Materials and Methods. Eighty-nine patients hospitalized...

  • DAMPs activating innate and adaptive immune responses in COPD. Pouwels, S D; Heijink, I H; ten Hacken, N HT; Vandenabeele, P; Krysko, D V; Nawijn, M C; van Oosterhout, A JM // Mucosal Immunology (1933-0219);Mar2014, Vol. 7 Issue 2, p215 

    Chronic obstructive pulmonary disease (COPD), a progressive lung disease characterized by sustained neutrophilic airway inflammation, is caused by chronic exposure to noxious stimuli, e.g., cigarette smoke. This chronic exposure can induce immunogenic cell death of structural airway cells,...

  • Adenosine Receptors As Promising Therapeutic Targets for Drug Development in Chronic Airway Inflammation. Polosa, Riccardo; Holgate, Stephen T. // Current Drug Targets;Jun2006, Vol. 7 Issue 6, p699 

    A growing body of evidence has emerged in support of a pro-inflammatory role for adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the airways such as asthma and COPD. The demonstration that adenosine enhances mast cell allergen-dependent activation, the notion that...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics