SUPPRESSION OF CYTOKINE-INDUCED NEUTROPHIL ACCUMULATION IN RAT MESENTERIC VENULES IN-VIVO BY GENERAL-ANESTHESIA

Most studies of neutrophil-endothelial interactions in vivo necessaril y require the use of general anesthetic agents which are well known to be immunosuppressive. By using whole-mount preparations of the rat me soappendix, we were able to study tumor necrosis factor alpha (TNF-alp ha) induced neutrophil adhesion to the mesenteric venular endothelium in vivo without necessarily using general anesthesia. TNF-alpha signif icantly increased venular-neutrophil accumulation in a dose-dependent manner; accumulation was markedly increased at 1, 2, and 4 h, but retu rned to baseline after 24 h. After these preliminary dose-response and time-course studies, we evaluated the influence of standard clinicall y effective doses of several commonly used anesthetic agents (thiopent al, pentobarbital, ketamine, alpha-chloralose, methoxyflurane, and hal othane) on the extent of neutrophil-venular accumulation induced 2 h a fter intraperitoneal injection of 0.4 mg/kg TNF-alpha, compared to una nesthetized rats. All general anesthetics tested, with the exception o f methoxyflurane, significantly suppressed this response. In most case s this suppression was striking (from 60 to 85%) such that a statistic ally significant proinflammatory response was obscured. Although metho xyflurane also tended to suppress this response to TNF-alpha, it was t he only agent that allowed the response to be clearly seen. Because an esthesia markedly suppresses cytokine-induced neutrophil-venular adhes ion, this model should provide an important complementary technique to the classical in vivo microcirculatory approaches which do necessaril y require general anesthesia.