Interferon (IFN)
therapy in humans often causes flu-like symptoms by an unknown mechanism.
Poly ICLC is a synthetic dsRNA and a
Toll-like receptor 3 (TLR3) agonist with a strong IFN-inducing ability. In this work, we analyzed the effect of
poly ICLC on pulmonary responses to
influenza and respiratory syncytial virus (
RSV) infections in the cotton rat (Sigmodon hispidus) model. Viral replication,
pulmonary inflammation, and expression of IFN, TLR, and
chemokines were monitored and compared.
Antiviral effect of
poly ICLC against influenza virus and RSV was best achieved at high
poly ICLC concentrations that, in the absence of
virus infection, induced a strong IFN response. The
antiviral doses of
poly ICLC, however, also increased
lung inflammation, an unexpected finding because of the reported
poly ICLC safety in BALB/c mice. Similarly, in contrast to murine model, pathology of
RSV infection was increased in cotton rats treated with
poly ICLC. Augmented
lung inflammation was accompanied by an earlier induction of IFN and TLR responses and a stronger
chemokine expression. Overall, these findings indicate significant association between
antiviral IFN action and
pulmonary inflammation and highlight important animal model-specific variations in the potential of IFN to cause pathology.