title: Effects of propofol on early and late cytokines in lipopolysaccharide-induced septic shock in rats.
abstract: OBJECTIVE
  It has been reported that the intravenous anesthetic propofol (PPF) has anti-inflammatory effects in vitro and in patients. The purpose of this study was to investigate whether PPF has anti-inflammatory effects in lipopolysaccharide (LPS)-induced septic shock by inhibiting the induction of pro-inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] and high mobility group box 1 (HMGB1) in rats.
  
  
  METHODS
  Thirty six male Wistar rats were randomly assigned to one of three groups (control group, PPF + LPS group and LPS group; n = 12 per group). Control group rats received a 0.9% NaCl solution (NS) by the tail vein. The PPF + LPS group rats received PPF (10 mg/kg bolus, followed by infusion at 10 mg/(kg·h) through a femoral vein catheter) 1 h before LPS (7.5 mg/kg) administration via the tail vein. The LPS group rats received injection of LPS (7.5 mg/kg) via the tail vein. Hemodynamic effects were recorded as well as mortality rates, and plasma cytokine con-centrations (TNF-α, IL-6, HMGB1) were measured for the 24-h observation period.
  
  
  RESULTS
  The mean arterial pressure and heart rate of the PPF + LPS group were more stable than those of the LPS group. The mortality at 24 h after the administration of the LPS injection was much higher in the LPS group (58.3%) compared to the PPF + LPS group (25.0%). Plasma concentrations of cytokines (IL-6 and TNF-α) and HMGB1 were significantly reduced in the PPF + LPS group compared to the LPS group (P < 0.05).
  
  
  CONCLUSIONS
  Pretreatment with PPF reduced the mortality rate of rats and attenuated the pro-inflammatory cytokine responses in an endotoxin shock model through an anti-inflammatory action inhibiting induction of HMGB1.
authors.affiliation: Department of Anesthesiology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, Jiangsu Province, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Hongguang
authors.initials: H
authors.lastname: Bao
authors.forename: Liu
authors.initials: L
authors.lastname: Han
authors.forename: Lele
authors.initials: L
authors.lastname: Liu
keywords: high mobility group box 1; interleukin-6; propofol; sepsis; tumor necrosis factor-α
references.citation: Anesth Analg. 1996 Apr;82(4):738-43
references.pmid: 8615490
references.citation: JAMA. 1995 Mar 22-29;273(12):934-41
references.pmid: 7884952
references.citation: Crit Care Med. 1997 Jul;25(7):1115-24
references.pmid: 9233735
references.citation: Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1768-73
references.pmid: 11734424
references.citation: Mini Rev Med Chem. 2005 Mar;5(3):241-5
references.pmid: 15777258
references.citation: N Engl J Med. 2003 Apr 17;348(16):1546-54
references.pmid: 12700374
references.citation: Mol Cell Biol. 1999 Aug;19(8):5237-46
references.pmid: 10409715
references.citation: J Clin Invest. 1993 Mar;91(3):1028-34
references.pmid: 8450032
references.citation: Tohoku J Exp Med. 2003 Jun;200(2):85-92
references.pmid: 12962405
references.citation: Anesth Prog. 2001 Spring;48(2):66-71
references.pmid: 11515950
references.citation: Int Immunopharmacol. 2010 Aug;10(8):967-77
references.pmid: 20669364
references.citation: J Exp Med. 2000 Aug 21;192(4):565-70
references.pmid: 10952726
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):12040-4
references.pmid: 8265667
references.citation: Science. 1999 Jul 9;285(5425):248-51
references.pmid: 10398600
references.citation: Anaesthesia. 1994 Jun;49(6):485-9
references.pmid: 8017590
references.citation: J Anesth. 2005;19(1):40-4
references.pmid: 15674515
references.citation: Anesth Analg. 2005 Mar;100(3):810-816
references.pmid: 15728072
references.citation: Curr Pharm Des. 2004;10(29):3639-49
references.pmid: 15579060
references.citation: Crit Care Med. 1996 Apr;24(4):584-9
references.pmid: 8612407
references.citation: Clin Exp Pharmacol Physiol. 2005 Jan-Feb;32(1-2):24-9
references.pmid: 15730430
references.citation: Lancet. 1999 Aug 7;354(9177):497-501
references.pmid: 10465189
references.citation: Shock. 2002 Jun;17(6):463-7
references.pmid: 12069181
references.citation: Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):149-56
references.pmid: 19948257
references.citation: Circ Shock. 1993 May;40(1):14-23
references.pmid: 8324886
references.citation: Mol Biol Rep. 2009 Nov;36(8):2345-51
references.pmid: 19190997
references.citation: Crit Care Med. 1989 Oct;17(10):975-8
references.pmid: 2791581
references.citation: Infect Immun. 1990 Jul;58(7):2375-82
references.pmid: 2114366
references.citation: Crit Care Med. 2000 Apr;28(4):1101-6
references.pmid: 10809290
references.citation: J Infect Dis. 1995 Jan;171(1):145-52
references.pmid: 7528250
references.citation: Surgery. 1999 Aug;126(2):389-92
references.pmid: 10455911
references.citation: J Immunol. 1983 Oct;131(4):1913-6
references.pmid: 6311900