A Drug That Prevents Lung Damage Protects Mice with Influenza Infection

A novel approach for treating infection by the influenza virus focuses on strengthening the small blood vessels in the lung of the victim so they do not leak fluids, which can lead to respiratory failure.

Seasonal influenza virus infections cause hundreds of thousands of deaths annually while viral mutation raises the threat of the emergence of a novel pandemic strain. Severe influenza virus infections are complicated by respiratory failure due to the development of microvascular leaks that lead to acute lung injury. Antiviral drugs exhibit limited efficacy unless administered early and may induce viral resistance. For these reasons targeting the host response directly has been proposed as a novel therapeutic strategy with the added potential benefit of not eliciting viral resistance.

To test the potential therapeutic benefits of enhancing lung endothelial barrier integrity, investigators at St. Michael's Hospital (Toronto, Canada) treated influenza infected mice with the drug Vasculotide. This drug is a synthetic peptide-based growth factor that targets Tie-2, a receptor on specialized cells of the hematopoietic and vascular systems. Tie-1 and Tie-2 comprise the cell-surface receptors that bind and are activated by the angiopoietins, (Ang1, Ang2, Ang3, and Ang4). The angiopoietins are protein growth factors required for the formation of blood vessels.

Results published in the June 5, 2015, online edition of the journal Scientific Reports, revealed that Vasculotide improved survival in mouse models of severe influenza, even if administered as late as 72 hours after infection. In one study 100% of infected mice died within one week, while more than 80% of a similar group treated with Vasculotide survived.

The benefits of the drug were observed using three strains of the virus and two strains of mice. The effect required Tie2, was independent of viral replication, and did not impair lung neutrophil recruitment.

Senior author Dr. Warren Lee, a cell biologist at St. Michael's Hospital, said, "While this research was conducted in mice, the results were exciting, since the drug was effective in two different strains of mice and three different strains of flu. Since the mechanism of blood vessels leaking into lungs is common throughout animals, I am optimistic the drug could be effective in animals other than mice, including humans."

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