Evidence for cytokine mediation of disease expression in adults experimentally infected with influenza A virus

J Infect Dis. 1999 Jul;180(1):10-4. doi: 10.1086/314823.


The roles of interleukin (IL)-6 and IL-8 in mediating the symptoms and signs of influenza A infection were examined. Adults were intranasally inoculated with a rimantadine-sensitive strain of influenza A HlNl virus and treated with rimantadine or placebo. Viral shedding, secretion weights, symptom scores, and concentrations of IL-6 and IL-8 in nasal lavage fluids were compared between treatment groups. Viral shedding was associated with increases in local and systemic symptoms, in expelled secretion weights, and in levels of IL-6 and IL-8. Compared with placebo, rimantadine treatment reduced viral shedding, systemic symptoms, and levels of IL-8. Days of viral shedding and IL-6 but not IL-8 concentrations were significantly correlated with the other measures of symptoms and signs. These data support a causal relationship between viral replication, cytokine production, and symptom expression, and they suggest that IL-6 may have a role in mediating symptom and sign expression during influenza A infection.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antiviral Agents / therapeutic use
  • Female
  • Humans
  • Influenza A virus / drug effects*
  • Influenza, Human / drug therapy*
  • Influenza, Human / immunology
  • Interleukin-6 / analysis*
  • Interleukin-8 / analysis*
  • Male
  • Middle Aged
  • Mucus / immunology
  • Nasal Lavage Fluid / immunology
  • Rimantadine / therapeutic use*
  • Statistics, Nonparametric


  • Antiviral Agents
  • Interleukin-6
  • Interleukin-8
  • Rimantadine