IL-6 trans-signalling in HPS and HFRS pathogenesis: a treatable target?

Hantaviruses cause two severe acute diseases; hantavirus pulmonary syndrome (HPS), and hemorrhagic fever with renal syndrome (HFRS). Fatality rates are 35-40% for HPS and up to 10% for HFRS, but no specific treatment or vaccine exists. HPS and HFRS are characterized by inflammation and increased vascular permeability.

However, the mechanisms behind hantavirus-caused disease are currently unknown,hampering the development of treatments.Recently, we reported that serum IL-6 levels correlate to HPS severity, and that the highest IL-6 levels were observed in patients with fatal outcome, i.e., in patients with fatal lung failure caused by increased vascular permeability.

This encouraged us to more in detail investigate the potential roles of IL-6 in hantavirus infection.

Strikingly, our preliminary findings in patients together with our preliminary results from in vitro studies suggest that IL-6 trans-signaling, acting on infected endothelial cells, is responsible for both inflammation and increased permeability.The purpose of this project is to increase our understanding of how hantaviruses cause severe disease.

Based on our data, we hypothesize that IL-6 trans-signaling is central for the pathogenesis in HPS and HFRS.

In more detail, we aim to identify and understand the role of IL-6 trans-signaling in hantavirus-induced inflammation and increased vascular permeability, with the ultimate aim to establish the basis for targeted therapies.