Elevated Serum Interleukin-8 Level as a Preferable Biomarker for Identifying Uncontrolled Asthma and Glucocorticosteroid Responsiveness

BACKGROUND: To explore the clinical significance of serum interleukin-8 (IL-8) level as a biomarker for uncontrolled asthma in order to improve our understanding of asthma phenotypes and facilitate the development of new therapeutic agents in the future. MATERIALS AND METHODS: A total of 246 uncontrolled asthma patients and 50 healthy controls were selected from an outpatient clinic during October 2015 and April 2016. The clinical data were collected, and the levels of IL-8, IL-6, tumor necrosis factor-α (TNF-α), and immunoglobulin (IgE) were measured in peripheral blood via ELISA assay. The level of serum IL-8 was compared between the glucocorticosteroid groups, receiving inhaled corticosteroids (ICs), oral corticosteroids (OCs), and intravenous corticosteroids (GCs), respectively. Changes in the serum IL-8 level were compared between asthmatics with good and poor glucocorticosteroid responsiveness. RESULTS: The serum IL-8 level in uncontrolled asthmatics (87.45 pg/mL; 5–7500) was significantly higher than that of the healthy controls (10.9 pg/mL; 6.8–39.65; P< 0.001). The increase in the serum IL-8 level above the normal range occurred in 58.13% of uncontrolled asthmatics. The area under curve (AUC) for serum IL-8 level, indicative of uncontrolled asthma, was 0.816 (95% CI, 0.7605 to 0.8721; P< 0.0001), which was greater than the AUC of fractional exhaled nitric oxide (AUC, 0.711; 95% CI, 0.6057 to 0.8153; P= .0188). The serum IL-8 level showed a significant positive relationship with blood neutrophil count (P= 0.0004), neutrophil percentage (P= 0.027), serum TNF-α protein (P< 0.0001), forced expiratory volume/forced vital capacity (FEV(1)/FVC) ratio (P< 0.05), and rate of FEV(1) change after bronchodilation. The level of IL-8 in patients requiring OCs or GCs treatment was significantly higher than that of ICs patients (186 and 235 pg/mL vs. 61 pg/mL; P< 0.0001). The reduction in the serum IL-8 level was more significant in asthmatic patients with good responsiveness (277 pg/mL (65.3–3124) to 67.8 pg/mL (5–1408); P< 0.0001), compared to those with poor responsiveness (218 pg/mL (64.8–7500) vs. 197 pg/mL (56.9–5238); P= 0.49). CONCLUSION: The increase in serum IL-8 level can be used as a preferable biomarker to identify asthma status and initial treatment in asthmatics. The change in IL-8 level also reflects the response to glucocorticosteroids in uncontrolled asthma. These exploratory results suggest an association between the pathophysiology, inflammation, and clinical outcomes of asthma. This raises the possibility of developing new agents for IL-8 inhibition and helps provide more precise and personalized asthma care.