Time Trends of Th1 and Th2 Cytokines in Induced Sputum of Asthmatic Subjects During Acute Upper Respiratory Viral Infections

FUNDAMENTALS: Many asthma exacerbations are caused by respiratory viral infections that induce the interplay between Th1 and Th2 immune responses. However, the time trends for Th1 and Th2 immune responses during these phenomena have not been well studied. OBJECTIVE: To identify possible mechanisms underlying the link between respiratory viral infections and asthma exacerbations. PATIENTS AND METHODS: We recruited 40 adults aged 21-58 years for 4 groups. A. Healthy, B. Healthy with viral infection, C. Mild to moderate asthma and D. Same as C, but with viral infection. Th1 and Th2 cytokines in induced sputum samples during the course of acute upper respiratory viral infections in otherwise healthy and asthmatic individuals were monitored. IL-4, IL-5 and IFN-γ were assayed by ELISA. Viral infection symptoms and asthma severity scores were monitored. Time trends were analyzed using linear mixed models. RESULTS: IL-4 and IL-5 levels in groups C and D were higher than in groups A and B. IFN-γ levels and viral infection symptoms scores in group B spiked by day 2 and rapidly declined by day 7, while in group D, IFN-γ and symptoms scores for viral infection and asthma peaked much later (days 3-5) and slowly declined. The ratios of IL-4 and IL-5 to IFN-γ in group D were significantly higher than in group C. CONCLUSIONS: Infection-induced asthma exacerbations may be due to impaired anti-viral Th1-immune responses. There appears to be a critical window of 3-5 days for therapeutic intervention.