Journal
NEUROIMMUNOMODULATION
Volume 29, Issue 4, Pages 306-316Publisher
KARGER
DOI: 10.1159/000520746
Keywords
Adrenal hormones; Cytokines; Hypothalamus; Neuroinflammation; Sepsis
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2015/12152-5]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) [001]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
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This study investigates the dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis in sepsis survivors. The results indicate that the HPA axis recovers soon after sepsis induction, with normal secretion of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) observed in both naive and sepsis survivor animals. The study also suggests that inflammatory mediators may play a role in the physiological response to sepsis.
Background: 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. Methods: 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. Results: Five days survivor animals showed increased plasma nitrate (p < 0.001) and interleukin (IL)-1 beta levels (p < 0.05) that were abolished in the 10 days survivors. In the hypothalamus of both survivors, the reverse was seen with IL-6 increased (p < 0.01), while IL-1 beta 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. Conclusion: 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.
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