title: Distinct effects of NPY13-36, a specific NPY Y2 agonist, in a model of rodent endotoxemia on leukocyte subsets and cytokine levels.
abstract: Even now, sepsis remains a major problem in modern clinical medicine, leading to systemic inflammatory response including altered leukocyte subset distribution and increased cytokine release. As immune cells are known to express NPY receptors, we investigated the effects of a specific NPY Y(2) receptor agonist (NPY(13-36)) and/or the corresponding Y(2) receptor antagonist BIIE0246 treatment on blood (by FACS analyses) and tissue (by immunohistochemistry) leukocyte subsets as well as on levels of IL-4, IL-6, IL-10, TNF-α, INF-γ (by Cytometric Bead Array) in healthy and acutely endotoxemic rats. Results show a significant decrease in blood monocytes after LPS challenge in endotoxemic control animals (by 93%), in endotoxemic NPY(13-36) treated animals (by 83%) and in endotoxemic BIIE0246 treated animals (by 88%) as compared to the corresponding healthy controls. Endotoxemic control animals showed a significant increase of TNF-α (by 98%) as compared to the healthy control group. A treatment with NPY(13-36) significantly stabilized TNF-α level in endotoxemic animals. This study indicates distinct subset- and cytokine-specific in vivo effects induced by an NPY Y(2) receptor specific treatment after a short-term LPS challenge.
authors.affiliation: Institute for Functional and Applied Anatomy, Hannover Medical School, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Stadler
authors.forename: Tina Phan
authors.initials: TP
authors.lastname: Le
authors.forename: Philipp
authors.initials: P
authors.lastname: Haas
authors.forename: Heike
authors.initials: H
authors.lastname: Nave
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D019446:Endotoxemia / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*
chemical_list: D001552:Benzazepines; D016207:Cytokines; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C062924:neuropeptide Y (13-36); C095889:neuropeptide Y2 receptor; D001120:Arginine; C403256:BIIE 0246