CYTOKINE RELEASE AS A MECHANISM MEDIATING IGIV ADVERSE REACTIONS

辅助性T细胞1型免疫应答与IL-12、IFN（和 细胞免疫反应。 这些反应可以由细菌引起 及其产物，特别是细菌DNA（bDNA）和脂多糖 （LPS）。这些产品可以刺激巨噬细胞释放其他 促炎细胞因子TNF α和IL-1 β。 血浆的制造 衍生物涉及非无菌的步骤， 细菌污染。 完整的细菌通过无菌 过滤，但这不会去除LPS或bDNA。 于是， 有兴趣看看这些细菌产物是否能诱导细胞因子 可能与给药后的不良事件相关 免疫球蛋白（IG）。 像完整的细菌一样，bDNA诱导了大量的 IL-12和IFN-γ，但这不是LPS的情况。 所有三 刺激物（细菌、bDNA和LPS）诱导IL-10分泌。 动力学 分析表明，细菌和bDNA以相同的速率诱导IL-10 LPS。 然而，尽管IL-12的产生在6-18 h达到峰值，但IL-10 产量继续保持高位。 这些动力学表明， IL-10可能调节对细菌的Th 1样细胞因子应答， bDNA IL-12对LPS的反应相对较差，但在 存在抗IL-10抗体。 这些结果证明 细菌成分能够产生细胞因子，这些细胞因子可能是 参与不良事件。 他们还认为，IL-10可能会抑制 这些不必要的回应。

T-helper type 1 immune responses are associated with IL-12, IFN( and cellular immune responses. These responses can be induced by bacteria and their products, notably, bacterial DNA (bDNA) and lipopolysaccharide (LPS). These products can stimulate macrophages to release other proinflammatory cytokines, TNFalpha and IL-1beta. Manufacture of plasma derivatives involves steps that are not aseptic and which can lead to bacterial contamination. The intact bacteria are removed by sterile filtration, but this does not remove LPS or bDNA. Thus it was of interest to see whether these bacterial products can induce cytokines that may be associated with adverse events following administration of immune globulin (Ig). Like intact bacteria bDNA induced large amounts of IL-12 and IFNgamma, but this was not the case with LPS. All three stimuli (bacteria, bDNA and LPS) induced IL-10 secretion. Kinetic analyses showed that the bacteria and bDNA induced IL-10 at the same rate as LPS. However, whereas IL-12 production peaked at 6-18 h, IL-10 production continued to remain elevated. These kinetics suggested that IL-10 may be modulating the Th1-like cytokine response to bacteria and bDNA. The relatively poor IL-12 response to LPS was enhanced in the presence of anti-IL-10 antibody. These results demonstrate that bacterial components have the ability to generate cytokines which may be involved in adverse events. They also suggest that IL-10 may dampen these unwanted responses.