Enhancing survival after ionizing radiation exposure through mitigation of pyroptosis.

• Pyroptosis, an inflammatory cell death, has been implicated in the pathogenesis of total body irradiation (TBI) so we investigated time course and cell type involvement of key mediators in a murine model. • Pyroptotic mediators were most highly expressed at day 3 post TBI with immune cells from ileum being preferentially activated. • We also investigated the effectiveness of MCC950, a potent pyroptosis inhibitor, in our murine model showing a survival benefit at 50 mg/kg regardless of sex. • Treatment with MCC950 showed elevations in full-length downstream mediator IL-1β in ileum and decreased levels of cleaved IL-1β in splenic tissue.