Squadrito F, Altavilla D, Ioculano M, Calapai G, Zingarelli B, Saitta A, Campo G M, Rizzo A, Caputi A P
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Circ Shock. 1992 Jul;37(3):236-44.
Splanchnic artery occlusion shock was induced in anesthetized rats by clamping splanchnic arteries for 45 min. Survival rate, serum and macrophage tumor necrosis factor (TNF-alpha), peritoneal macrophage phagocytosis, and killing activities were evaluated. Shocked rats died within 2 hr, whilst all sham-shocked rats survived more than 6 hr. Serum and macrophage TNF-alpha was undetectable in sham-shocked rats while shocked rats exhibited increased serum (110 +/- 5 U/ml 90 min after release of occlusion) and macrophage levels (122 +/- 4.5 U/ml 90 min after release of occlusion) of TNF-alpha. Furthermore, splanchnic artery occlusion shock produced cardiovascular changes, reduced macrophage phagocytosis (23 +/- 4.6%) and killing (6 +/- 1.1%) activities, and induced a massive necrosis of the ileum. A passive immunization with a hyperimmune serum containing antibodies against murine TNF-alpha significantly protected rats from the lethal effects of splanchnic artery occlusion shock, lowered serum TNF-alpha (6 +/- 2.1 U/ml), and completely reverted the impairment in peritoneal macrophage phagocytosis (48 +/- 4.8%) and killing (13 +/- 1.5%) activities. In addition passive immunization had beneficial effects on the cardiovascular changes occurring during splanchnic artery occlusion shock and prevented necrosis of the ileum induced by this model of shock. By contrast, pretreatment with polymyxin B, an "antiendotoxin" antibiotic, did not modify the lethal effects and the TNF-alpha production induced by splanchnic artery occlusion shock. Furthermore, endotoxin was undetectable in the blood of splanchnic artery occlusion shocked rats. These findings are consistent with the involvement of TNF-alpha in splanchnic artery occlusion shock and suggest that the cytokine represents an important mediator of non-septic shock.
通过夹闭内脏动脉45分钟，在麻醉大鼠中诱导内脏动脉闭塞性休克。评估存活率、血清和巨噬细胞肿瘤坏死因子（TNF-α）、腹腔巨噬细胞吞噬作用及杀伤活性。休克大鼠在2小时内死亡，而所有假手术休克大鼠存活超过6小时。假手术休克大鼠血清和巨噬细胞中未检测到TNF-α，而休克大鼠在解除夹闭后90分钟血清TNF-α水平升高（110±5 U/ml），巨噬细胞TNF-α水平也升高（122±4.5 U/ml）。此外，内脏动脉闭塞性休克引起心血管变化，降低巨噬细胞吞噬作用（23±4.6%）和杀伤活性（6±1.1%），并导致回肠大量坏死。用含抗鼠TNF-α抗体的超免疫血清进行被动免疫可显著保护大鼠免受内脏动脉闭塞性休克的致死作用，降低血清TNF-α水平（6±2.1 U/ml），并完全逆转腹腔巨噬细胞吞噬作用（48±4.8%）和杀伤活性（13±1.5%）的损伤。此外，被动免疫对内脏动脉闭塞性休克期间发生的心血管变化有有益作用，并可防止该休克模型诱导的回肠坏死。相比之下，用“抗内毒素”抗生素多粘菌素B预处理并未改变内脏动脉闭塞性休克诱导的致死作用和TNF-α产生。此外，在内脏动脉闭塞性休克大鼠血液中未检测到内毒素。这些发现与TNF-α参与内脏动脉闭塞性休克一致，并表明该细胞因子是非感染性休克的重要介质。
