Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense

Abstract

To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1β, IL-2, IL-6, IL-8, IFN-∅, TGF-β, and TNF-α in nasal lavage fluid, plasma, and serum obtained serially from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlated these levels with various measures of infection and illness severity. We found that IL-6 and IFN-α levels in nasal lavage fluids peaked early (day 2) and correlated directly with viral titers, temperature, mucus production, and symptom scores. IL-6 elevations were also found in the circulation at this time point. In contrast, TNF-α responses peaked later (day 3 in plasma, day 4 in nasal fluids), when viral shedding and symptoms were subsiding. Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower respiratory symptoms, which also occurred late. None of IL-1β, IL-2, or TGF-β levels increased significantly. These data implicate IL-6 and IFN- α as key factors both in symptom formation and host defense in influenza.