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

To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1 beta, IL-2, IL-6, IL-8, IFN-alpha, TGF-beta, and TNF-alpha 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-alpha 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-alpha 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-1 beta, IL-2, or TGF-beta levels increased significantly, These data implicate IL-6 and IFN-alpha as key factors both in symptom formation and host defense in influenza.