title: Remifentanil attenuates human neutrophils activation induced by lipopolysaccharide.
abstract: The purpose of the present study was to investigate the effect of various opioids including remifentanil, sufentanil, alfentanil and fentanyl on human neutrophil activation induced by lipopolysaccharide (LPS) and to reveal the correlation involving the activation of cytokines and mitogen-activated protein kinases (MAPKs). Neutrophils from human blood were incubated with various concentrations of opioids with LPS. We measured protein levels for tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-8 after 4 h incubation period. To clarify the intracellular signaling pathway, we measured the levels of phosphorylation of p38, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase. We also measured the levels for cytokines and MAPKs to reveal the effects of several opioid receptor subtype antagonists on remifentanil with LPS. In the present experiment, only remifentanil could attenuate activation of human neutrophils exposed to LPS. In particular, remifentanil decreased activation of intracellular signaling pathways, including p38 and ERK1/2, and expression of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-8. Especially the decreased activation of cytokines and MAPKs was significantly reverted by a kappa-opioid receptor antagonist on remifentanil with LPS. These results demonstrate that remifentanil can attenuate human neutrophils activations induced by LPS and a kappa-opioid receptor be probably involved in these anti-inflammatory effects mediated by remifentanil.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Hyejin
authors.forename: Li
authors.initials: L
authors.lastname: Mei
authors.forename: Lee
authors.initials: L
authors.lastname: Seongheon
authors.forename: Jeong
authors.initials: J
authors.lastname: Cheolwon
authors.forename: Kim
authors.initials: K
authors.lastname: Seokjai
authors.forename: Bea
authors.initials: B
authors.lastname: Hongbeom
authors.forename: Kim
authors.initials: K
authors.lastname: Minsun
authors.forename: Chung
authors.initials: C
authors.lastname: Sungsu
authors.forename: Kwak
authors.initials: K
authors.lastname: Sanghyun
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D000077208:Remifentanil; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010880:Piperidines; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077208:Remifentanil