Provocative decompression causes diffuse vascular injury in mice mediated by microparticles containing interleukin-1β

Thom, Stephen R., Veena M. Bhopale, Kevin Yu, and Ming Yang. "Provocative decompression causes diffuse vascular injury in mice mediated by microparticles containing interleukin-1β." Journal of Applied Physiology (2018).

Inflammatory mediators are known to be elevated in association with decompression from elevated ambient pressure, but their role in tissue damage or overt decompression sickness is unclear. Circulating microparticles (MPs) are also know to increase and because interleukin (IL)-1β is packaged within these particles, we hypothesized that IL-1β was responsible for tissue injuries. Here, we demonstrate that elevations of circulating MPs containing up to 9-fold higher concentrations of IL-1β occur while mice are exposed to high air pressure (790 kPa), whereas smaller particles carrying proteins specific to exosomes are not elevated. MPs number and intra-particle IL-1β concentration increase further over 13 hours post-decompression. MPs also exhibit intra-particle elevations of tumor necrosis factor-α, caspase-1, inhibitor of κB kinase -β and -γ, and elevated IL-6 is adsorbed to the surface of MPs. Contrary to lymphocytes, neutrophil NLRP3 inflammasome oligomerization and cell activation parameters occur during high pressure exposure, and additional evidence for activation are manifested post-decompression. Diffuse vascular damage, while not apparent immediately post-decompression, was present 2 hours later and remained elevated for at least 13 hours. Prophylactic administration of an IL-1β receptor inhibitor or neutralizing antibody to IL-1β inhibited MPs elevations, increases of all MPs-associated pro-inflammatory agents, and vascular damage. We conclude that an auto-activation process triggered by high pressure stimulates MPs production and concurrent inflammasome activation, and IL-1β is a proximal factor responsible for further cytokine production and decompression-associated vascular injuries.

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