Introduction:
Cardiac arrest (CA) is associated with high mortality and morbidity, which is in part due to infectious complications developed in CA patients. Infection complications, particularly pneumonia, occur in approximately 60% of CA patients. Given this high incidence, we hypothesized that after CA, the immune system is impaired, which increases the susceptibility of CA patients to potential infections. Therefore, in this study, we systematically examined the immune response in the brain and peripheral immune organs after CA.
Methods:
Mice were subjected to CA and cardiopulmonary resuscitation (CA/CPR). Flow cytometry, ELISA, immunohistochemistry, and quantitative PCR were used to analyze the immune response in various post-CA organs.
Results:
First, we characterized the time course of the immune response in the spleen after CA/CPR. CA/CPR induced significant changes in all major immune cell populations. Notably, B cell frequencies decreased, while T cell frequencies increased, in various organs on day 3 post-CA. Further, the levels of pro-inflammatory cytokines, eg IL-6, were markedly increased in the blood and brain after CA. Critically, we found that the lymphocyte counts in the spleen and thymus were dramatically lower in CA mice than in sham mice. Interestingly, CA/CPR caused progressive atrophy of the spleen and thymus. Since it has been shown that CA/CPR alters activity of the hypothalamic-pituitary-adrenal (HPA) axis, we speculated that CA-induced atrophy of lymphoid organs is mediated by the HPA axis. Thus, we treated CA mice with RU486, a glucocorticoid receptor antagonist. Indeed, this treatment reversed CA-induced organ atrophy and mitigated immune cell depletion, both in the thymus and spleen.
Conclusions:
We provided for the first time evidence that CA/CPR rapidly induced a systemic inflammatory response followed by impairment of the immune system, which eventually led to a massive loss of immune cells in the peripheral immune organs. This CA-induced immunodeficiency appears to be mediated by dysregulation of the HPA axis. Our findings here may be of high clinical significance, considering the high incidence of infectious complications in CA patients and their detrimental effects on CA outcome.
Vitamin E and stress
