非人灵长类动物感染性休克的研究:抗肿瘤坏死因子抗体治疗的病理生理反应关系。

Circulatory shock Pub Date : 1994-12-01
L B Hinshaw, T E Emerson, A C Chang, M Duerr, G Peer, M Fournel
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引用次数: 0

摘要

据报道,抗肿瘤坏死因子抗体治疗可有效预防注射致死性大肠杆菌的狒狒发病和死亡。在大肠杆菌致死性输注后早期给予抗体,治疗动物存活,器官组织病理学不存在。本研究探讨了抗体剂量、病理生理和休克存活率之间的关系。当抗体剂量降低时,肺、肾、肾上腺、脾脏和肝脏受到损伤,表现为血管充血、出血、水肿和组织坏死增加。生存也受到影响。15 mg/kg抗体处理的所有动物均存活,如前所述;7.5 mg/kg的剂量不足60%;5.0 mg/kg剂量下9%存活,1.5 mg/kg剂量下全部死亡。血清白细胞介素-6 (IL-6)浓度随抗体剂量的降低而显著升高。IL-6浓度的增加与大肠杆菌给药后发病率和死亡率的增加有关。
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Study of septic shock in the non-human primate: relationship of pathophysiological response to therapy with anti-TNF antibody.

Therapy with anti-TNF antibody is reported to be effective in preventing morbidity and mortality in baboons given lethal infusions of Escherichia coli. Treated animals survived, and organ histopathology was absent when antibody was administered early after lethal infusions of E. coli. The present study explored the relationship between antibody dosage, pathophysiology, and survivability from shock. When antibody dose was decreased lungs, kidneys, adrenals, spleen, and liver were injured as shown by increased vascular congestion, hemorrhage, edema, and necrosis of tissues. Survival was also affected. All animals treated with 15 mg/kg antibody survived as reported earlier; less than 60% survived with 7.5 mg/kg; 9% survived with 5.0 mg/kg, and all died with 1.5 mg/kg. Serum concentrations of interleukin-6 (IL-6) increased markedly as dose of antibody decreased. The increases in concentrations of IL-6 were associated with increases in morbidity and mortality following E. coli administration.

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