CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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

M A Dentener¹, R Louis², R H E Cloots¹, M Henket², E F M Wouters¹

¹ Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Respiratory Medicine, Maastricht University, Maastricht, The Netherlands
² Department of Pneumology, CHU Sart-Tilman, University of Liege, Belgium

Correspondence to:
M A Dentener PhD
Department of Respiratory Medicine, University Hospital Maastricht, P O Box 5800, 6202 AZ Maastricht, The Netherlands; Mieke.Dentener{at}pul.unimaas.nl

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 (TNF) 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 TNF 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). TNF was measured by ELISA.

Results: Sputum cells produced spontaneously high levels of TNF but were unresponsive to LPS. Sputum cells from COPD patients (both steroid free and steroid treated) produced significantly less TNF than cells from healthy non-smoking subjects (p = 0.017 and p = 0.001, respectively). In contrast, blood cells produced TNF only in response to LPS. No differences were observed in TNF production by blood cells between the patient groups and the control groups. HA (both fragments) partially blocked LPS (1 ng/ml) induced TNF release by blood cells from all study groups, whereas TNF production by sputum cells was not influenced by HA.

Conclusion: These data indicate a difference between local and systemic TNF production. Sputum cells of patients with COPD produced less TNF than controls, which could contribute to impaired local defence. An inhibitory effect of HA on TNF release in blood cells was observed which was similar in both patients and controls.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; HA, hyaluronan; IL, interleukin; LPS, lipopolysaccharide; TNF, tumour necrosis factor

Keywords: chronic obstructive pulmonary disease; hyaluronan; inflammation; sputum cells; tumour necrosis factor (TNF)

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