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Pituitary Adenylate Cyclase-Activating Polypeptide Prevents Mortality Caused by Septic Peritonitis in Mice.
- Source :
-
ImmunoHorizons [Immunohorizons] 2020 Apr 17; Vol. 4 (4), pp. 191-200. Date of Electronic Publication: 2020 Apr 17. - Publication Year :
- 2020
-
Abstract
- The purpose of this study was to investigate whether pituitary adenylate cyclase-activating polypeptide (PACAP) prevents mortality due to sepsis in mice. Mice were given PACAP at designated time points before or after cecal ligation and puncture (CLP), and organ injury and mortality were investigated. Serum inflammatory and anti-inflammatory cytokine levels were assessed after CLP. Plasma corticosterone and adrenocorticotropic hormone levels were also measured. Isolated tissue macrophages (Mfs) were incubated with or without PACAP, and production of cytokines was measured. Activation of NF-κB was investigated in tissue Mfs isolated from CLP animal in the presence and absence PACAP in vitro. PACAP treatment significantly prevented acute lung injury and mortality after CLP. Plasma endotoxin levels and bacterial load were not different between PACAP-treated and nontreated groups. Increased serum TNF-α and HMGB1 levels in animals treated with vehicle were significantly blunted in PACAP-treated animals after CLP. Furthermore, serum IL-10 levels were significantly greater in the PACAP-treated group compared with the vehicle group. Production of HMGB1 and TNF-α by isolated hepatic Mfs was significantly inhibited in the presence of PACAP, whereas production of IL-10 by isolated hepatic Mfs and interstitial lung Mfs was significantly increased. Plasma corticosterone and adrenocorticotropic hormone levels were significantly greater in the animals treated with PACAP compared with vehicle after CLP. Activation of NF-κB was significantly inhibited by PACAP in the hepatic Mfs compared with other tissue Mfs. PACAP prevents mortality due to septic peritonitis by inhibiting inflammation via NF-κB activation and possible effects on the brain.<br /> (Copyright © 2020 The Authors.)
- Subjects :
- Acute Lung Injury mortality
Adrenocorticotropic Hormone blood
Animals
Cells, Cultured
Corticosterone blood
Cytokines blood
Disease Models, Animal
HMGB1 Protein metabolism
Macrophages drug effects
Macrophages immunology
Mice
Mice, Inbred C57BL
NF-kappa B metabolism
Peritonitis blood
Peritonitis mortality
Sepsis blood
Sepsis mortality
Signal Transduction drug effects
Treatment Outcome
Tumor Necrosis Factor-alpha metabolism
Acute Lung Injury etiology
Acute Lung Injury prevention & control
Peritonitis complications
Peritonitis drug therapy
Pituitary Adenylate Cyclase-Activating Polypeptide administration & dosage
Sepsis complications
Sepsis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2573-7732
- Volume :
- 4
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- ImmunoHorizons
- Publication Type :
- Academic Journal
- Accession number :
- 32303568
- Full Text :
- https://doi.org/10.4049/immunohorizons.1900044