Introduction: Inflammation is associated with the development of pulmonary vascular remodelling in pulmonary arterial hypertension (PAH). While some viral pathogens have been implicated in PAH, we do not know if prior activation of antiviral immunity in the lungs is an important driver of the disease.

Aim: To investigate if prior lung inflammation induced by double-stranded RNA, an activator of antiviral immunity, alters severity of pulmonary hypertension (PH) in the sugen-hypoxia (SuHx) mouse model of PH.

Methods: C57BL/6J mice were administered single or repeated (two doses, 8 days apart) intranasal (IN) instillations of synthetic dsRNA (100mg poly(I:C)). Pulmonary immune responses were quantified via lavage fluid immune cell counts, cytokine analysis and histology. Next, one (n=14) or two doses (n=4-5) of IN poly(I:C) were instilled and PH was induced using SuHx following inflammation resolution (9 days after poly(I:C)). PH was assessed by cardiac catheterisation.

Results: Relative to a single IN poly(I:C) instillation, neutrophil infiltration and cytokine responses were reduced 24 hours after a second IN dose. The severity of PH, assessed by right ventricular systolic pressure, was not altered in SuHx mice previously exposed to IN poly(I:C) compared to saline controls whether mice had been exposed to single or repeated doses of poly(I:C).

Conclusions: Our data suggest that prior activation of antiviral immunity alone does not influence the haemodynamic severity of PH in this mouse model. Vascular remodelling analysis is in progress. Future work could include a multi-hit model, using mice with genetic susceptibility to pulmonary hypertension.