Highlights
• Hantavirus triggers the kallikrein–kinin system, driving severe capillary leak.
• In vitro data show that bradykinin directly disrupts endothelial barrier function.
• Two clinical cases support targeting the bradykinin pathway with icatibant.
Abstract
A recent multi-country hantavirus outbreak associated with a cruise ship underscores the urgent need to understand the mechanisms driving severe vascular leakage and multi-organ failure. While disease severity is largely attributed to a dysregulated host immune response and intense cytokine surge, the precise molecular mediators remain incompletely defined. Laboratory evidence indicates that hantavirus infection activates the factor XII–dependent kallikrein–kinin system, leading to elevated bradykinin production and subsequent endothelial barrier dysfunction. This translational mechanism is tentatively supported by two clinical case reports where severe hantavirus infections were successfully treated with the bradykinin receptor antagonist icatibant. We hypothesize that exaggerated bradykinin signalling drives the vascular leak phenotype, making the kallikrein–kinin pathway a compelling therapeutic target. Ultimately, effectively combating hantavirus-induced vascular permeability may require a multi-faceted approach combining targeted bradykinin inhibition with broader immunomodulatory strategies.
Source:
Link: https://www.sciencedirect.com/science/article/abs/pii/S016524782600074X?via%3Dihub
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