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

TLDR

The study aimed to measure cytokine levels in nasal lavage, plasma, and serum from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlate them with infection and illness severity. Cytokine concentrations of IL‑1β, IL‑2, IL‑6, IL‑8, IFN‑α, TGF‑β, and TNF‑α were serially quantified in these fluids. IL‑6 and IFN‑α peaked early (day 2) and correlated with viral titers, temperature, mucus, and symptom scores, whereas TNF‑α and IL‑8 peaked later (days 3–6) and were associated with symptom resolution and lower‑respiratory symptoms; IL‑1β, IL‑2, and TGF‑β did not rise, indicating IL‑6 and IFN‑α are key factors in 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.