Interleukin-32, not reduced by salmeterol/fluticasone propionate in smokers with chronic obstructive pulmonary...

The interleukin (IL)-32/tumor necrosis factor (TNF) a pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease (COPD) inflammation. Inhaled corticosteroids (ICS) in combination with long-acting β2-agonists (LABA) have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain.

Patients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate (SF; Seretide, GlaxoSmithKline) Diskus (50/500 µg twice daily) or ipratropium bromide/salbutamol (IS; Combivent, Boehringer Ingelheim) MDI (42 µg/240 µg quartic daily) for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-α, the number of neutrophils and eosinophils were measured.

Following 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-α in sputum (P = 0.004) was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance (P = 0.028) but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George's respiratory questionnaire in both the SF (P = 0.004) and IS (P = 0.030) treatment groups, but no evidence of improvement in lung function was observed in either group.

The sputum TNF-α and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.