Imbalances Between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) are potentially important in Chronic Obstructive Pulmonary Disease (COPD), but little is known of the relationships between these cytokines and their antagonists in disease compared with healthy controls. It is unclear if concentrations relate to disease severity. The study aimed to investigate these relationships and to assess the potential activity of each cytokine in the context of their antagonists. Plasma cytokines, soluble receptors, and cell counts were measured in patients with stable COPD and age-matched healthy controls (n = 15 for both) daily for 5 days; these mediators were also measured in corresponding sputum samples from the COPD patients. COPD patients had significantly reduced concentrations of the antagonists, IL-1sRII, and IL-1RA compared with controls. In COPD, IL-1 beta exceeded its antagonists and correlated significantly with BMI and FEV1, while plasma IL-1RA correlated positively with BMI but negatively with sputum IL-1 beta, neutrophil, and macrophage counts and smoking history. TNF alpha antagonists exceeded agonists in both groups and did not correlate with COPD severity. Endogenous IL-1 beta antagonists appear reduced in COPD. Furthermore, IL-1 beta correlated with clinical aspects of disease severity, suggesting that IL-1 beta may play a critical role in COPD. Given the relevant concentrations and binding affinities, it is likely that TNF alpha has limited activity in stable COPD.