Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease: a pilot study

BACKGROUND: Chronic obstructive pulmonary disease (COPD) with cachexia is characterized by inflammation reflected by increased levels of tumor necrosis factor-alpha (TNF-alpha). Objectives: In this study, infliximab, an anti-TNF-alpha antibody, was evaluated for its effects on systemic (plasma) and local (exhaled breath condensate, EBC) inflammation in cachectic patients with COPD. Also, baseline levels of new inflammatory markers were compared to control subjects. METHODS: Sixteen cachectic patients with moderate to severe COPD were examined for inflammatory status at baseline and compared to 25 control subjects. Patients were randomized (1:1) to receive infliximab (5 mg/kg) or placebo at weeks 0, 2 and 6. Patients were evaluated at weeks 8 and 12 and followed through week 26. RESULTS: EBC analysis revealed increased levels of several novel inflammatory markers, including macrophage migration inhibitory factor, IL-12, RANTES and sICAM-1, in patients with COPD compared to controls. EBC levels of inflammatory markers were unchanged in patients receiving infliximab. In addition, systemic levels of acute-phase proteins (C-reactive protein, fibrinogen and lipopolysaccharide-binding protein), IL-6 and soluble TNF receptor (sTNFR) 55 had not changed at weeks 8 or 12. Small increases in circulating levels of sTNFR75, myeloperoxidase and Clara cell protein 16 were seen at week 8, but not at week 12. CONCLUSIONS: In this small study, infliximab did not produce an observable decrease in local inflammation in cachectic patients with COPD and had minor effects on systemic inflammation. The detection of new inflammatory markers in EBC can help to further characterize local inflammatory processes in COPD.