Aguillón J C, Ferreira V, Núñez E, Paredes L, Molina M C, Colombo A, Hermosilla T, Ferreira A
Departamento de Medicina Preventiva Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile.
Scand J Immunol. 1996 Dec;44(6):551-5. doi: 10.1046/j.1365-3083.1996.d01-345.x.
Immunologically, the septic shock is a natural model of immunomediated vascular pathology where the interaction between cytokines and the endothelium mediates the syndrome and lethality. Tumour necrosis factor (TNF), a non-species-specific cytokine, has outstanding pleiotropic activities as an important mediator of the septic shock syndrome. In rabbits, passive immunization with anti-lipopolysaccharide (LPS) polyclonal antibodies prior to the intravenous (i.v.) injection of LPS inhibits the haemorrhagic necrotic lesion characteristic of the local Shwartzman reaction (an excellent localized in vivo correlate of the septic shock). Paradoxically, tested in an ex vivo assay (short-term whole human blood culture, stimulated with LPS), these antibodies mediated an increase in TNF production by mononuclear phagocytes and, in the rabbit model, they induced an increase in body temperature, as compared with the pre-immune reagent. Although anchoring of immune complexes containing LPS to receptors (Fc or C4b-C3b) on circulating monocytes may facilitate the access of LPS to these cells, access to localized, LPS-sensitized macrophages may be impaired. Consequently inhibition of the local Shwartzman reaction and increased TNF production in the ex vivo system were observed. Concordantly, the higher temperature in the passively immunized animals may be a consequence of a higher, immune complex-induced, systemic TNF production. These experimental results suggest that the use of anti-LPS immunoglobulins, as a potential immunotherapy for septic shock syndrome in vertebrates, may lead to increased TNF production, with adverse effects such as the pyrogenic.
从免疫学角度来看，脓毒症休克是免疫介导的血管病理的自然模型，其中细胞因子与内皮细胞之间的相互作用介导了该综合征和致死性。肿瘤坏死因子（TNF）是一种非物种特异性细胞因子，作为脓毒症休克综合征的重要介质，具有显著的多效性活性。在兔子中，在静脉注射脂多糖（LPS）之前用抗LPS多克隆抗体进行被动免疫，可抑制局部施瓦茨曼反应（脓毒症休克的一种出色的体内局部相关反应）的出血性坏死病变特征。矛盾的是，在体外试验（用LPS刺激的短期全血培养）中进行测试时，这些抗体介导单核吞噬细胞产生的TNF增加，并且在兔子模型中，与免疫前试剂相比，它们导致体温升高。尽管含有LPS的免疫复合物与循环单核细胞上的受体（Fc或C4b - C3b）结合可能有助于LPS进入这些细胞，但进入局部的、对LPS敏感的巨噬细胞的途径可能会受到损害。因此，观察到局部施瓦茨曼反应受到抑制，并且体外系统中TNF产生增加。与此一致，被动免疫动物中较高的体温可能是免疫复合物诱导的全身TNF产生增加的结果。这些实验结果表明，使用抗LPS免疫球蛋白作为脊椎动物脓毒症休克综合征的潜在免疫疗法，可能会导致TNF产生增加，并产生诸如发热等不良反应。
