title: Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock.
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.
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig-University, Rudolf-Buchheim-Str. 7, D-35392 Giessen, Germany. reginald.matejec@chiru.med.uni-giessen.de
authors.forename: Reginald
authors.initials: R
authors.lastname: Matejec
authors.forename: Friederike
authors.initials: F
authors.lastname: Kayser
authors.forename: Frauke
authors.initials: F
authors.lastname: Schmal
authors.forename: Florian
authors.initials: F
authors.lastname: Uhle
authors.forename: Rolf-Hasso
authors.initials: RH
authors.lastname: Bödeker
authors.forename: Hagen
authors.initials: H
authors.lastname: Maxeiner
authors.forename: Julia Anna
authors.initials: JA
authors.lastname: Kolbe
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D006785:Hospitals, University; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000521:alpha-MSH / Q000097:blood; D001615:beta-Endorphin / Q000031:analogs & derivatives / Q000097:blood; D008083:beta-Lipotropin / Q000097:blood
chemical_list: D006684:HLA-DR Antigens; D000521:alpha-MSH; D001615:beta-Endorphin; C035101:N-acetyl-beta-endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008083:beta-Lipotropin
keywords: Alpha melanocyte stimulating hormone (α-MSH); Corticotropin releasing hormone (CRH); Human leukocyte antigen-DR (HLA-DR); Proopiomelanocortin (POMC); Septic shock; Tumor necrosis factor-α (TNF-α)