Suppression of cytokine-induced neutrophil accumulation in rat mesenteric venules in vivo by general anesthesia.
Most studies of neutrophil-endothelial interactions in vivo necessarily require the use of general anesthetic agents which are well known to be immunosuppressive. By using whole-mount preparations of the rat mesoappendix, we were able to study tumor necrosis factor alpha (TNF-alpha) induced neutrophil adhesion to the mesenteric venular endothelium in vivo without necessarily using general anesthesia. TNF-alpha significantly increased venular-neutrophil accumulation in a dose-dependent manner, accumulation was markedly increased at 1, 2, and 4 h, but returned to baseline after 24 h. After these preliminary dose-response and time-course studies, we evaluated the influence of standard clinically effective doses of several commonly used anesthetic agents (thiopental, pentobarbital, ketamine, alpha-chloralose, methoxyflurane, and halothane) on the extent of neutrophil-venular accumulation induced 2 h after intraperitoneal injection of 0.4 mg/kg TNF-alpha, compared to unanesthetized rats. All general anesthetics tested, with the exception of methoxyflurane, significantly suppressed this response. In most cases this suppression was striking (from 60 to 85%) such that a statistically significant proinflammatory response was obscured. Although methoxyflurane also tended to suppress this response to TNF-alpha, it was the only agent that allowed the response to be clearly seen. Because anesthesia markedly suppresses cytokine-induced neutrophil-venular adhesion, this model should provide an important complementary technique to the classical in vivo microcirculatory approaches which do necessarily require general anesthesia.
Miller
L S
LS
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
Morita
Y
Y
Rangan
U
U
Kondo
S
S
Clemens
M G
MG
Bulkley
G B
GB
D000768:Anesthesia, General / Q000009:adverse effects*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005069:Evaluation Studies as Topic; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D014409:Tumor Necrosis Factor-alpha