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 format ion 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 volun teers 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 flu ids peaked early (day 2) and correlated directly with viral titers, te mperature, mucus production, and symptom scores, IL-6 elevations were also found in the circulation at this time point, In contrast, TNF-alp ha responses peaked later (day 3 in plasma, day 4 in nasal fluids), wh en viral shedding and symptoms were subsiding, Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower r espiratory 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 defe nse in influenza.