title: 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-1beta, 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-1beta, 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.
authors.affiliation: University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: F G
authors.initials: FG
authors.lastname: Hayden
authors.forename: R
authors.initials: R
authors.lastname: Fritz
authors.forename: M C
authors.initials: MC
authors.lastname: Lobo
authors.forename: W
authors.initials: W
authors.lastname: Alvord
authors.forename: W
authors.initials: W
authors.lastname: Strober
authors.forename: S E
authors.initials: SE
authors.lastname: Straus
mesh_terms: D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D017817:Nasal Lavage Fluid / Q000276:immunology; D014838:Volunteers
chemical_list: D016207:Cytokines