IL-18 is a proinflammatory cytokine implicated in COPD pathophysiology, causing pulmonary inflammation and emphysema in murine models. IL-18 receptor expression is increased on alveolar macrophages in COPD.1 IL-18 levels are elevated in serum and sputum of stable COPD patients. We hypothesised that airway and systemic IL-18 concentrations increase further at exacerbation.Methods
Sputa and sera prospectively collected from the London COPD cohort were analysed using ELISA (eBioscience®, Vienna). Patients had an FEV1=80% predicted and FEV1/FVC ratio=0.7. Baseline was defined as at least 6 weeks after, and 2 weeks before, an exacerbation. An exacerbation was defined as an increase for two consecutive days in respiratory symptoms, with at least one major symptom (dyspnoea, sputum purulence or volume) plus another major or minor (wheeze, cold, sore throat or cough) symptom. Exacerbation frequency was calculated from daily diary cards collected over the previous 12 months. When unavailable, patient's recall of exacerbations over the preceding year was used. Frequent exacerbators had ≥2 exacerbations in the preceding year, infrequent exacerbators <2.Results
94 COPD patients had serum analysed, of whom 48 also had sputum analysed. 60% were male, mean age was 71.6 years (SD 8.5), mean FEV1 predicted 50.6% (18.1). Sputum IL-18 levels increased significantly from baseline to exacerbation (median 1.46 log10 pg/ml (IQR 0.96–2.01) vs 1.95 (0.96–2.23), n=48, p=0.023, Abstract P119 figure 1). However, serum IL-18 concentrations were not significantly greater at exacerbation compared to paired baseline levels (median 2.17 log10 pg/ml (1.97–2.37) vs 2.08 (1.91–2.36), n=31, p=0.299).There was no correlation between baseline serum IL-18 concentrations and exacerbation frequency (n=94, ρ=0.096, p=0.357) or FEV1% predicted (n=93, ρ=0.081, p=0.443). No significant difference was found in baseline serum IL-18 concentrations between frequent and infrequent exacerbators (median 148 pg/ml (95–235; n=46) vs 120 (78–219; n=48), p=0.431). There was no correlation between baseline serum IL-18 concentrations and paired sputum levels (n=42, ρ=−0.149, p=0.348).Conclusions
Sputum but not serum IL-18 increases at COPD exacerbation. Treatment options for exacerbations are limited and there is a need for novel anti-inflammatories. The results of this study suggest IL-18 as a potential target for exacerbation therapy.