Differences in Organ Dysfunction in Endotoxin-Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin

Abstract

Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis, the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction, and therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion, and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, and cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed. In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin-tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.