Corticosterone and Adrenocorticotrophic Hormone Secretion Is Recovered after Immune Challenge or Acute Restraint Stress in Sepsis Survivor Animals

Abstract

<b><i>Background:</i></b> Clinical and experimental studies report a dysregulation of hypothalamus-pituitary-adrenal (HPA) axis during sepsis that causes impairment in hormone secretion in the late phase contributing for the pathophysiology of the disease. However, it is unclear whether this alteration persists even after the disease remission. <b><i>Methods:</i></b> We evaluated the effect of an immune challenge or restraint stress on the hormone secretion of HPA axis in sepsis survivor rats. Sepsis was induced by cecal ligation-puncture (CLP) surgery. Naive or animals that survive 5 or 10 days after CLP were submitted to lipopolysaccharide (LPS) injection or restraint stress. After 60 min, blood was collected for plasma nitrate, cytokines, adrenocorticotropic hormone (ACTH), and corticosterone (CORT) and brain for synaptophysin and hypothalamic cytokines. <b><i>Results:</i></b> Five days survivor animals showed increased plasma nitrate (<i>p</i> &#x3c; 0.001) and interleukin (IL)-1β levels (<i>p</i> &#x3c; 0.05) that were abolished in the 10 days survivors. In the hypothalamus of both survivors, the reverse was seen with IL-6 increased (<i>p</i> &#x3c; 0.01), while IL-1β did not show any alteration. Synaptophysin expression was reduced in both survivors and did not change after any stimuli. Only the LPS administration increased plasma and/or inflammatory mediators levels in both groups (survivors and naive) being apparently lower in the survivors. There was no difference in the increased secretion pattern of ACTH and CORT observed in the naive and sepsis survivor animals submitted to immune challenge or restraint stress. <b><i>Conclusion:</i></b> We conclude that the HPA axis is already recovered soon after 5 days of sepsis induction responding with normal secretion of ACTH and CORT when required.