PURPOSE: Ketamine is reported to suppress production of proinflammatory cytokines and activity of nuclear factor-kappa B (NF-kappaB) after lipopolysaccharide (LPS) stimulation. Our study was designed to investigate the effects of ketamine on pulmonary inflammatory responses and survival in a clinically relevant model of polymicrobial sepsis, induced by cecal ligation and puncture (CLP). METHODS: After the induction of sepsis or sham-operation, animals were treated with ketamine (0.5, 5 or 10 mg/kg) or saline (10 ml/kg) at 3h after operation. At 6 h post-operation, the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6, activity of NF-kappaB, expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of the lungs were measured. And the mortality was recorded for 7 days. RESULTS: TNF-alpha and IL-6 production, NF-kappaB activity, TLR2 and TLR4 expression in rat lungs were increased after CLP. Ketamine at the doses of 5 mg/kg and 10 mg/kg suppressed CLP-induced elevation of TNF-alpha and IL-6 production, NF-kappaB activity and TLR2 expression. Ketamine 0.5, 5 and 10 mg/kg inhibited TLR4 expression in sepsis. Ketamine 5mg/kg and 10 mg/kg after CLP improved the survival of rats. CONCLUSIONS: Ketamine at sub-anesthetic doses could suppress the production of inflammatory cytokines such as TNF-alpha and IL-6, attenuate NF-kappaB activity, and inhibit TLR2 and TLR4 expression in polymicrobial sepsis. These anti-inflammatory effects of ketamine may correlate with improved survival in sepsis.
PURPOSE:Ketamine is reported to suppress production of proinflammatory cytokines and activity of nuclear factor-kappa B (NF-kappaB) after lipopolysaccharide (LPS) stimulation. Our study was designed to investigate the effects of ketamine on pulmonary inflammatory responses and survival in a clinically relevant model of polymicrobial sepsis, induced by cecal ligation and puncture (CLP). METHODS: After the induction of sepsis or sham-operation, animals were treated with ketamine (0.5, 5 or 10 mg/kg) or saline (10 ml/kg) at 3h after operation. At 6 h post-operation, the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6, activity of NF-kappaB, expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of the lungs were measured. And the mortality was recorded for 7 days. RESULTS:TNF-alpha and IL-6 production, NF-kappaB activity, TLR2 and TLR4 expression in rat lungs were increased after CLP. Ketamine at the doses of 5 mg/kg and 10 mg/kg suppressed CLP-induced elevation of TNF-alpha and IL-6 production, NF-kappaB activity and TLR2 expression. Ketamine 0.5, 5 and 10 mg/kg inhibited TLR4 expression in sepsis. Ketamine 5mg/kg and 10 mg/kg after CLP improved the survival of rats. CONCLUSIONS:Ketamine at sub-anesthetic doses could suppress the production of inflammatory cytokines such as TNF-alpha and IL-6, attenuate NF-kappaB activity, and inhibit TLR2 and TLR4 expression in polymicrobial sepsis. These anti-inflammatory effects of ketamine may correlate with improved survival in sepsis.
Authors: Ahmet Tekin; Tevfik Küçükkartallar; Serdar Türkyilmaz; Ayhan Dinckan; Hasan Esen; Burhan Ateş; Hüseyin Yilmaz; Adil Kartal Journal: Inflammation Date: 2008-08 Impact factor: 4.092
Authors: Eric S Schwenk; Basant Pradhan; Rohit Nalamasu; Lucas Stolle; Irving W Wainer; Michael Cirullo; Alexander Olsen; Joseph V Pergolizzi; Marc C Torjman; Eugene R Viscusi Journal: Curr Pain Headache Rep Date: 2021-07-16
Authors: Helmut Trimmel; Raimund Helbok; Thomas Staudinger; Wolfgang Jaksch; Brigitte Messerer; Herbert Schöchl; Rudolf Likar Journal: Wien Klin Wochenschr Date: 2018-01-10 Impact factor: 1.704