The Effects of Remifentanil on Expression of High Mobility Group Box 1 in Septic Rats.
High mobility group box 1 (HMGB1) is a pivotal mediator of sepsis progression. Remifentanil, an opioid agonist, has demonstrated anti-inflammatory effects in septic mice. However, it is not yet known whether remifentanil affects the expression of HMGB1. We investigated the effects of remifentanil on HMGB1 expression and the underlying mechanism in septic rats. Forty-eight male Sprague-Dawley rats were randomly divided into 3 groups; a sham group, a cecal ligation and puncture (CLP) group, and a CLP with remifentanil treatment (Remi) group. The rat model of CLP was used to examine plasma concentrations of proinflammatory cytokines, tissue HMGB1 mRNA and the activity of nuclear factor (NF)-κB in the liver, lungs, kidneys, and ileum. Pathologic changes and immunohistochemical staining of NF-κB in the liver, lungs, and kidneys tissue were observed. We found that remifentanil treatment suppressed the level of serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α 6 hours after CLP, and serum HMGB1 24 hours after CLP. HMGB1 mRNA levels and the activity of NF-κB in multiple organs decreased by remifentanil treatment 24 hours after CLP. Remifentanil treatment also attenuated nuclear expression of NF-κB in immunohistochemical staining and mitigated pathologic changes in multiple organs. Altogether, these results suggested that remifentanil inhibited expression of HMGB1 in vital organs and release of HMGB1 into plasma. The mechanism was related to the inhibitory effect of remifentanil on the release of proinflammatory cytokines and activation of NF-κB.
Department of Anesthesiology and Pain Medicine, Saint Vincent's Hospital, The College of Medicine, The Catholic University of Korea, Suwon, Korea.
Kwon Hui
http://orcid.org/0000-0002-3965-7603
KH
Seo
Department of Anesthesiology and Pain Medicine, Saint Vincent's Hospital, The College of Medicine, The Catholic University of Korea, Suwon, Korea.
Jin Woo
http://orcid.org/0000-0002-7290-0361
JW
Choi
Department of Anesthesiology and Pain Medicine, Saint Vincent's Hospital, The College of Medicine, The Catholic University of Korea, Suwon, Korea.
Hong Soo
http://orcid.org/0000-0002-6812-1955
HS
Jung
Department of Anesthesiology and Pain Medicine, Saint Vincent's Hospital, The College of Medicine, The Catholic University of Korea, Suwon, Korea.
Hansol
http://orcid.org/0000-0001-8261-0811
H
Yoo
Department of Anesthesiology and Pain Medicine, Saint Vincent's Hospital, The College of Medicine, The Catholic University of Korea, Suwon, Korea. joojd@catholic.ac.kr.
Jin Deok
http://orcid.org/0000-0002-4365-7091
JD
Joo
D000410:Alanine Transaminase / Q000097:blood; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000077208:Remifentanil; D018805:Sepsis / Q000378:metabolism / Q000473:pathology* / Q000662:veterinary; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000701:Analgesics, Opioid; D024243:HMGB1 Protein; D015850:Interleukin-6; D016328:NF-kappa B; D010880:Piperidines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D000410:Alanine Transaminase; D000077208:Remifentanil
HMGB1 Protein; Inflammation; NF-κB; Remifentanil; Sepsis