RHINOVIRUS STIMULATION OF INTERLEUKIN-6 IN-VIVO AND IN-VITRO - EVIDENCE FOR NUCLEAR FACTOR KB-DEPENDENT TRANSCRIPTIONAL ACTIVATION

To further understand the biology of rhinovirus (RV), we determined wh ether IL-6 was produced during RV infections and characterized the mec hanism by which RV stimulates lung cell IL-6 production. In contrast t o normals and minimally symptomatic volunteers, IL-6 was detected in t he nasal washings from patients who developed colds after RV challenge . RV14 and RV1A, major and minor receptor group RVs, respectively, wer e potent stimulators of IL-6 protein production in vitro. These effect s were associated with significant increases in IL-6 mRNA accumulation and gene transcription. RV was also a potent stimulator of IL-6 promo ter-driven luciferase activity. This stimulation was modestly decrease d by mutation of the nuclear factor (NF)-IL-6 site and abrogated by mu tation of the NF-kappa B site in this promoter. An NF-kappa B-DNA bind ing activity, mediated by p65, p50, and p52 NF-kappa B moieties, was r apidly induced in RV-infected cells. Activator protein 1-DNA binding w as not similarly altered. These studies demonstrate that IL-6 is produ ced during symptomatic RV infections, that RVs are potent stimulators of IL-6 elaboration, and that RV stimulation of IL-6 production is med iated by an NF-kappa B-dependent transcriptional stimulation pathway. IL-6 may play an important role in the pathogenesis of RV infection, a nd NF-kappa B activation is likely to be an important event in RV-indu ced pathologies.