Differences in local versus systemic TNFalpha production in COPD: inhibitory effect of hyaluronan on LPS induced blood cell TNFalpha release.
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 alpha (TNFalpha) 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 TNFalpha 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). TNFalpha was measured by ELISA.


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


CONCLUSIONS
These data indicate a difference between local and systemic TNFalpha production. Sputum cells of patients with COPD produced less TNFalpha than controls, which could contribute to impaired local defence. An inhibitory effect of HA on TNFalpha release in blood cells was observed which was similar in both patients and controls.
Dentener
M A
MA
Nutrition and Toxicology Research Institute Maastricht, Department of Respiratory Medicine, University Hospital Maastricht, P O Box 5800, 6202 AZ Maastricht, The Netherlands. Mieke.Dentener@pul.unimaas.nl
Louis
R
R
Cloots
R H E
RH
Henket
M
M
Wouters
E F M
EF
D000328:Adult; D000368:Aged; D001773:Blood Cells / Q000378:metabolism*; D001991:Bronchitis; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D013183:Sputum / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014797:Vital Capacity / Q000502:physiology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid