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Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock.
- Source :
-
Peptides [Peptides] 2013 Sep; Vol. 47, pp. 133-41. Date of Electronic Publication: 2013 Jul 25. - Publication Year :
- 2013
-
Abstract
- Little is known about interactions between immune and neuro-endocrine systems in patients with septic shock. We therefore evaluated whether the corticotropin-releasing hormone (CRH) and/or proopiomelanocortin (POMC) derivatives [ACTH, β-endorphin (β-END), β-lipotropin (β-LPH), α-melanocyte stimulating hormone (α-MSH) or N-acetyl-β-END (Nac-β-END)] have any influences on monocyte deactivation as a major factor of immunosuppression under septic shock conditions. Sixteen patients with septic shock were enrolled in a double-blind, cross-over and placebo controlled clinical study; 0.5μg/(kgbodyweighth) CRH (or placebo) were intravenously administered for 24h. Using flow cytometry we investigated the immunosuppression in patients as far as related to the loss of leukocyte surface antigen-DR expression on circulating monocytes (mHLA-DR). ACTH, β-END immunoreacive material (IRM), β-LPH IRM, α-MSH and Nac-β-END IRM as well as TNF-α and mHLA-DR expression were determined before, during and after treatment with CRH (or placebo). A significant correlation between plasma concentration of α-MSH and mHLA-DR expression and an inverse correlation between mHLA-DR expression and TNF-α plasma level were found. Additionally, a significant increase of mHLA-DR expression was observed 16h after starting the CRH infusion; 8h later, the mHLA-DR expression had decreased again. Our results indicate that the up-regulation of mHLA-DR expression after CRH infusion is not dependent on the release of POMC derivatives. From the correlation between plasma concentration of α-MSH and mHLA-DR expression, we conclude that in patients with septic shock the down-regulation of mHAL-DR expression is accompanied by the loss of monocytic release of α-MSH into the cardiovascular compartment.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Adrenocorticotropic Hormone blood
Aged
Cross-Over Studies
Double-Blind Method
Female
Gene Expression drug effects
HLA-DR Antigens immunology
Hospitals, University
Humans
Infusions, Intravenous
Intensive Care Units
Male
Middle Aged
Monocytes drug effects
Monocytes immunology
Monocytes pathology
Prospective Studies
Shock, Septic drug therapy
Shock, Septic immunology
Shock, Septic pathology
alpha-MSH blood
beta-Endorphin analogs & derivatives
beta-Endorphin blood
beta-Lipotropin blood
Corticotropin-Releasing Hormone administration & dosage
HLA-DR Antigens genetics
Monocytes metabolism
Shock, Septic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5169
- Volume :
- 47
- Database :
- MEDLINE
- Journal :
- Peptides
- Publication Type :
- Academic Journal
- Accession number :
- 23891702
- Full Text :
- https://doi.org/10.1016/j.peptides.2013.07.013