Effects of ketamine on pulmonary inflammatory responses and survival in rats exposed to polymicrobial sepsis.
OBJECTIVE
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.
Yu
Min
M
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China.
Shao
Danbing
D
Yang
Rong
R
Feng
Xiaomei
X
Zhu
Sihai
S
Xu
Jianguo
J
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D015996:Survival Rate
D016207:Cytokines; D007649:Ketamine