Differences in local versus systemic TNF alpha production in COPD: inhibitory effect of hyaluronan on LPS induced blood cell TNF alpha 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 (TNF alpha) 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 alpha 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 alpha was measured by ELISA. Results: Sputum cells produced spontaneously high levels of TNF alpha but were unresponsive to LPS. Sputum cells from COPD patients (both steroid free and steroid treated) produced significantly less TNF alpha than cells from healthy non-smoking subjects (p = 0.017 and p = 0.001, respectively). In contrast, blood cells produced TNF alpha only in response to LPS. No differences were observed in TNF alpha production by blood cells between the patient groups and the control groups. HA (both fragments) partially blocked LPS (1 ng/ml) induced TNF alpha release by blood cells from all study groups, whereas TNF alpha production by sputum cells was not influenced by HA. Conclusion: These data indicate a difference between local and systemic TNFa production. Sputum cells of patients with COPD produced less TNFa than controls, which could contribute to impaired local defence. An inhibitory effect of HA on TNF alpha release in blood cells was observed which was similar in both patients and controls.