Mortality of Septic Mice Strongly Correlates With Adrenal Gland Inflammation
| Autor: | Waldemar Kanczkowski, Bertram Scheller, Lars Heerdegen, Stefan R. Bornstein, Nguyen Tran, Ajith Kantharajah, Kai Zacharowski, Stefan Dröse, Carla Jennewein |
|---|---|
| Přispěvatelé: | University of Zurich, Jennewein, Carla |
| Rok vydání: | 2016 |
| Předmět: |
Male
Hypothalamo-Hypophyseal System medicine.medical_specialty Interleukin-1beta 10265 Clinic for Endocrinology and Diabetology Pituitary-Adrenal System Physiology 610 Medicine & health Inflammation Adrenocorticotropic hormone Critical Care and Intensive Care Medicine Sepsis Mice Random Allocation chemistry.chemical_compound Adrenocorticotropic Hormone Corticosterone Internal medicine Adrenal Glands Adrenal insufficiency Animals Medicine Cecum Ligation Interleukin-6 Tumor Necrosis Factor-alpha business.industry Septic shock Adrenal gland medicine.disease Shock Septic Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology chemistry Tumor necrosis factor alpha medicine.symptom 2706 Critical Care and Intensive Care Medicine business Adrenal Insufficiency |
| Zdroj: | Critical Care Medicine. 44:e190-e199 |
| ISSN: | 0090-3493 |
| Popis: | OBJECTIVES Sepsis and septic shock are commonly present in the ICU and accompanied by significant morbidity, mortality, and cost. The frequency of secondary adrenal insufficiency in sepsis remains open to debate and a challenge to identify and treat appropriately. Animal models of sepsis using genetic or surgical initiation of adrenal insufficiency resulted in increased mortality, but the mechanisms are still unclear. The present study investigates the impact of adrenal inflammation in septic mice challenged with cecal ligation and puncture. DESIGN Prospective experimental study. SETTING University laboratory. SUBJECTS C57BL/6N wild-type mice. INTERVENTIONS Sepsis, induced by cecal ligation and puncture for 24 and 48 hours. MEASUREMENTS AND MAIN RESULTS Both septic and control mice were carefully monitored (every 30 min) for up to 48 hours and divided into survivors and nonsurvivors. We observed a significant and massive increase of interleukin-6, interleukin-1β, and tumor necrosis factor-α in adrenal protein extracts of nonsurvivors compared with sham animals and survivors. This pattern was partly reflected in liver and lung but not in plasma samples. Notably, a significant increase in nonsurvivors compared with survivors was only found for lung interleukin-6. In line with these findings, we detected a higher degree of leukocyte infiltration and hemorrhage in the adrenal glands of deceased mice. Evaluation of the hypothalamic-pituitary-adrenal axis response in these animals revealed an increase of adrenocorticotropic hormone, which was only partly reflected in the corticosterone level. Notably, using the adrenocorticotropic hormone stimulation test, we found an impaired adrenocorticotropic hormone response, particularly in nonsurvivors, which significantly correlated with the number of infiltrated leukocytes. CONCLUSIONS Cecal ligation and puncture-induced murine sepsis induces a strong inflammatory response in the adrenal glands, which is accompanied by cell death and hemorrhage. Our data suggest that mortality and adrenal incapacitation are associated with the degree of adrenal inflammation, thereby underscoring the importance of adrenal function on survival. |
| Databáze: | OpenAIRE |
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