Abstract
Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial arrest event. However, among this growing patient population, morbidity and mortality rates remain strikingly high. This has been attributed to post-CA syndrome of which an imbalanced immune response is a crucial component. Using a murine CA model, we have shown that a profound immunosuppressive phase, characterized by severe lymphopenia, ensues following the initial pro-inflammatory response after CA. In the current study, we found that T and B lymphopoiesis was greatly impaired, as evidenced by the rapid and marked depletion of double-positive T cells and pre-B cells in the thymus and bone marrow, respectively. Our data then demonstrated that pharmacologic suppression of glucocorticoid signaling after CA significantly attenuated lymphopoiesis impairment, thereby mitigating post-CA lymphopenia. Lastly, we showed that specific deletion of the glucocorticoid receptor in T or B cells largely prevented the CA-induced depletion of immature lymphocyte populations in the thymus or bone marrow, respectively. Together, our findings indicate that glucocorticoid signaling mediates post-CA impairment of lymphopoiesis, a key contributor to post-CA immunosuppression.