Abstract 18007: Role of Interferon Lambda in Influenza-Induced Exacerbation of Atherosclerosis

Abstract

Introduction and Hypothesis: Influenza infection is a significant public health and economic threat around the world. Although pneumonia is the most common complication associated with influenza, there are several clinical reports demonstrating increased risk for cardiovascular disease. In influenza infection type I, type II and type III IFNs play an indispensable role in controlling the virus. In atherosclerosis, type I and type II IFNs promote atherosclerosis by inducing chemokines from macrophages and vascular endothelial cells. Studies have shown that the influenza infection exacerbates atherosclerosis. However, there are no studies determining the role of type III IFNs on influenza-induced exacerbation of atherosclerosis. In this study, we hypothesize that the type III IFN (IFNL3) may play a protective role in atherosclerosis. Methods: ApoE -/- mice were fed with a high-fat diet (HFD) containing 42% Kcal fat (Teklad) for 11 weeks. Mice were then infected with influenza A/PR/8/34 (H1N1) (100 pfu) and treated with recombinant IFNL3 by oropharyngeal (O/P) aspiration or intraperitoneal (I/P) injection, and weight loss, and gene expression of inflammatory cytokines and chemokines were measured. In another study, HFD-fed ApoE -/- and ApoE -/- IFNLR1 -/- mice were infected with influenza, and the disease outcomes were measured as described above. Results and Conclusions: IFNL3 treatment decreased influenza-induced weight loss in ApoE -/- mice during the early phase (4-6 days) of influenza infection. Further, IFNL3 treatment decreased gene expression levels of IL-6 and CCL2 in the aorta in influenza-infected ApoE -/- mice. Based on these findings, it seems likely that INFL3 plays a protective role in acute influenza-induced exacerbation of atherosclerosis. However, ApoE -/- IFNLR1 -/- mice recovered body weight faster than wild-type mice suggesting a detrimental role for IFNL after acute infection. These data show that IFNLR plays a protective role during the early phase of influenza infection and potentially a pathological role during the recovery phase of influenza infection.