Abstract 308: Corticosteroid Therapy Benefits Septic Mice With Adrenal Insufficiency but Harms Septic Mice Without Adrenal Insufficiency

Abstract

Rationale: Corticosteroid (CS) therapy is frequently used in septic patients. However, the efficacy of CS therapy is highly controversial. The heterogeneity of septic patients, the technical difficulties in identifying adrenal insufficiency and a lack of adrenal insufficiency animal model present significant barriers to address this longstanding clinical issue. Objectives: In this study, we utilized scavenger receptor BI (SR-BI) null mice as the first relative adrenal insufficiency animal model to evaluate the efficacy of CS therapy and assess the pathogenesis caused by adrenal insufficiency. Methods: Cecal ligation and puncture (CLP) was conducted on SR-BI-/- and wild type control mice, and then CS was administered 2 or 18h post CLP. Measurements and Main Results: We demonstrated that CS supplementation protects against CLP-induced sepsis in SR-BI-/- mice but causes more septic death in wild type controls. Importantly, we identified a cocktail of CS that provides more efficient protection than an individual CS, and the septic mice could be rescued 18h post CLP by the CS cocktail; we further demonstrated that adrenal insufficiency impairs both innate and adaptive immunity. Conclusions: This preclinical study provides a proof-of-concept that corticosteroid benefits septic patients with adrenal insufficiency but harms septic patients without adrenal insufficiency, and suggests that it is necessary to determine the status of adrenal insufficiency and only prescribe corticosteroid for septic patients with adrenal insufficiency.