Early Induction of Proinflammatory Cytokine and Type I Interferon mRNAs Following Newcastle Disease Virus, Poly [rI:rC], or Low-Dose LPS Challenge of the Mouse

Abstract

Numerous cytokines induce symptoms characteristic of the flu syndrome common to acute viral infections. To better characterize the cytokine mRNA profile associated with the early phase of this syndrome, we examined the induction of cytokine mRNAs in spleens of mice 1, 2, and 4 h following intraperitoneal inoculation of Newcastle disease virus (NDV). The reverse transcriptase-polymcrase chain reaction was used to detect mRNAs for mouse proinflammatory cytokines [interleukin (IL)-lα, IL-1β, IL-6, tumor necrosis factor-α (TNF-α), macrophage colony-stimulating factor (M-CSF), and interferon (IFN)-γ] and type I IFNs (IFN-α4 and IFN-β). We observed a rapid (within 2 h) induction of most of these cytokine mRNAs in the mouse spleen following challenge with live NDV or the viral simulant poly[rI:rC]. IL-1β, M-CSF, and IFN-γ mRNAs were also induced by heat-inactivated NDV, suggesting the possibility of endotoxin contamination of the virus (confirmed by Limulus lysate assay). Examination of cytokine induction by comparable doses of lipopolysaccharide indicated that endotoxin contamination could account for the cytokine mRNA-inducing activity of the heat-inactivated virus. These studies point to a critical control (heat-inactivated virus) for viral cytokine studies. In addition, they indicate that certain cytokine mRNAs (IL-lα, IL-6, M-CSF, IFN-γ, IFN-α, and IFN-β) are rapidly induced in the spleen when live virus is inoculated intraperitoneally, independently of contaminating endotoxin.