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

The roles of interleukin (IL)-6 and IL-8 in mediating the symptoms and sign s of influenza A infection were examined. Adults were intranasally inoculat ed with a rimantadine-sensitive strain of influenza A HINI virus and treate d with rimantadine or placebo. Viral shedding, secretion weights, symptom s cores, and concentrations of IL-6 and IL-8 in nasal lavage fluids were comp ared between treatment groups. Viral shedding was associated with increases in local and systemic symptoms; in expelled secretion weights, and in leve ls of IL-6 and IL-8, Compared with placebo, rimantadine treatment reduced v iral shedding, systemic symptoms, and levels of IL-8. Days of viral sheddin g and IL-6 but not IL-8 concentrations were significantly correlated with t he other measures of symptoms and signs. These data support a causal relati onship between viral replication, cytokine production, and symptom expressi on, and they suggest that IL-6 may have a role in mediating symptom and sig n expression during influenza A infection.