Kumar A, Thota V, Dee L, Olson J, Uretz E, Parrillo J E
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
J Exp Med. 1996 Mar 1;183(3):949-58. doi: 10.1084/jem.183.3.949.
Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This depression is associated with the presence of a circulating myocardial depressant substance with physical characteristics consistent with cytokines. The present study utilized an in vitro myocardial cell assay to examine the role of various human recombinant cytokines, including tumor necrosis factor (TNF)alpha and interleukin (IL)1beta, in depression of cardiac myocyte contractile function induced by serum from humans with septic shock. The extent and velocity of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed loop video tracking system. Individually, TNF-alpha and IL-1beta each caused significant concentration-dependent depression of maximum extent and peak velocity of myocyte shortening in vitro. In combination, TNF-alpha and IL-1beta induced depression of myocardial cell contractility at substantially lower concentrations consistent with a synergistic effect. Using immunoabsorption, removal of both TNF-alpha and IL-1beta (but not either alone) from the serum of five patients with acute septic shock and marked reversible myocardial depression resulted in elimination of serum myocardial depressant activity. IL-2, -4, -6, -8, -10, and interferon gamma failed to cause significant cardiac myocyte depression over a wide range of concentrations. These data demonstrate that TNF-alpha and IL-1beta cause depression of myocardial cell contraction in vitro and suggest that these two cytokines act synergistically to cause sepsis-associated myocardial depression in humans.
先前的研究已证实在临床和实验性脓毒性休克中存在心肌抑制。这种抑制与一种循环心肌抑制物质的存在有关，该物质的物理特性与细胞因子一致。本研究利用体外心肌细胞试验，来检测各种人类重组细胞因子，包括肿瘤坏死因子（TNF）α和白细胞介素（IL）1β，在脓毒性休克患者血清诱导的心肌细胞收缩功能抑制中的作用。通过闭环视频跟踪系统对组织培养中电刺激的大鼠心肌细胞的收缩程度和速度进行量化。单独来看，TNF-α和IL-1β各自在体外均引起心肌细胞缩短的最大程度和峰值速度显著的浓度依赖性抑制。联合使用时，TNF-α和IL-1β在实质上更低的浓度下即诱导心肌细胞收缩力抑制，这与协同效应一致。通过免疫吸附法，从五名患有急性脓毒性休克且伴有明显可逆性心肌抑制的患者血清中去除TNF-α和IL-1β（但不是单独去除其中任何一种），导致血清心肌抑制活性消除。IL-2、-4、-6、-8、-10和干扰素γ在广泛的浓度范围内未能引起明显的心肌细胞抑制。这些数据表明，TNF-α和IL-1β在体外引起心肌细胞收缩抑制，并提示这两种细胞因子协同作用导致人类脓毒症相关的心肌抑制。
