Basta M, Kirshbom P, Frank M M, Fries L F
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
J Clin Invest. 1989 Dec;84(6):1974-81. doi: 10.1172/JCI114387.
Studies were performed in in vitro and in vivo models to assess the effect of intravenous immunoglobulin (IVIG) on the development of acute complement-mediated tissue damage. IVIG significantly increased the duration of survival and frequently prevented the death of guinea pigs injected with anti-Forssman antiserum to cause lethal Forssman shock; no control animal treated with albumin and/or maltose vehicle survived. The most pronounced effect was achieve by delivering IVIG as one slow injection at 1,800 mg/kg 3 h before Forssman shock was elicited. Infusion of guinea pig IgG at the same dosage was similarly protective. A strong positive correlation was found between IgG plasma levels and survival time in guinea pigs treated with graded doses of IVIG. Therapy itself did not affect C3 and C4 levels nor the capacity to activate these components. In vitro studies showed almost complete inhibition of C3 uptake onto IgG-sensitized erythrocytes using serum from an IVIG-treated animal. We suggest that supraphysiologic levels of IVIG act in part by preventing active C3 fragments from binding to target cells. Infusion of high dose IVIG may be a rational approach to modulating acute, complement-dependent tissue damage in a variety of diseases in man.
我们开展了体外和体内模型研究，以评估静脉注射免疫球蛋白（IVIG）对急性补体介导的组织损伤发展的影响。IVIG显著延长了豚鼠的存活时间，并常常能防止注射抗福斯曼抗血清引发致命性福斯曼休克的豚鼠死亡；而接受白蛋白和/或麦芽糖赋形剂治疗的对照动物无一存活。在引发福斯曼休克前3小时，以1800 mg/kg的剂量缓慢单次注射IVIG，效果最为显著。以相同剂量输注豚鼠IgG也具有类似的保护作用。在接受不同剂量IVIG治疗的豚鼠中，IgG血浆水平与存活时间之间存在强正相关。治疗本身并不影响C3和C4水平，也不影响激活这些成分的能力。体外研究表明，使用IVIG治疗动物的血清，几乎能完全抑制C3附着到IgG致敏的红细胞上。我们认为，超生理水平的IVIG部分作用机制是阻止活性C3片段与靶细胞结合。输注高剂量IVIG可能是调节人类多种疾病中急性补体依赖性组织损伤的一种合理方法。
