CYTOKINE RELEASE AS A MECHANISM MEDIATING IGIV ADVERSE REACTIONS

细胞因子释放作为介导免疫球蛋白IV不良反应的机制 巴兹尔·戈尔丁，医学博士，OBRR血浆衍生品实验室医生 T辅助细胞可以根据不同的子集被划分 它们在刺激后分泌的细胞因子。因此Tho细胞分泌IL-4 Th1细胞分泌IL-2，Th2细胞产生IL-4，Th1细胞分泌IL-2。 IL-5。除T细胞外，单核/巨噬细胞还分泌细胞因子 如IL-12、TNFa、IL-1等。这些细胞因子在 免疫反应，但也与不良反应有关 在使用免疫球蛋白(IG)和T细胞抗体后 用来诱导免疫抑制。我们研究了这些细胞因子在 小鼠对不同结合物的免疫应答。多肽或蛋白质 与热灭活的流产布鲁氏菌(BA)和 锁孔帽状血蓝蛋白(KLH)。BA诱导IL-12和IFNG，而KLH 诱生IL-4。因此，引起的免疫球蛋白同型图谱相应 对细胞因子的影响，从而使KLH免疫与 IgG1和GT；IgG2a比值，而BA引起IgG2a和GT；IgG1。类似的模式也是 观察BA与卵清蛋白(OVA)和明矾联合给药的情况。 与单独给予OVA+明矾相比，BA和OVA+的组合 明胶与IL-12、IFNG的mRNA和蛋白诱导有关。这个 卵子+明矾后观察到的同型图谱是高滴度的IgG1 而在BA存在的情况下，以IgG2a为主，而IgG1和 免疫球蛋白E水平受到抑制。还研究了BA对人类的影响 培养中的细胞。已有研究表明，它能诱导人T细胞产生干扰素。 BA诱导人单核细胞产生IL-12，表现为p40 m RNA和 蛋白。细胞培养上清液诱导产生功能性IL-12 BA刺激的单核细胞导致T细胞分泌IFNG，这可能 可通过添加抗IL-12抗体来阻断。BA也增加了 B7.1和B7.2在人单核细胞上的表达这些分子是 共刺激分子参与刺激T细胞。免疫球蛋白 研究表明，这些制剂可以诱导人IL-1、TNFa和IL-6的分泌 单核细胞。这种能力由于这些准备工作的通过而被取消了。 在多粘菌素柱上，被证明可以将脂多糖去除为 用微量变形细胞测定法测定。这些研究表明， 免疫球蛋白制剂中含有少量的内毒素可诱导细胞因子 这可能解释了经常观察到的副作用，如发烧发冷， 还有头痛。

Cytokine Release as a Mechanism Mediating IGIV Adverse Reactions Basil Golding, M.D., Medical Officer, Plasma Derivatives Laboratory, OBRR T helper cell can be divided into different subsets based on the cytokines they secrete following stimulation. Thus ThO cells secrete IL-4 and IFNg, Th1 cells release IL-2 and IFNg and Th2 cells produce IL-4, and IL-5. In addition to T cells, monocytes/macrophages secrete cytokines such as IL-12, TNFa and IL-1. These cytokines play important roles in immune responses but have also been implicated in adverse effects following the use of immunoglobulins (IG) and antibodies against T cells used to induce immunosuppression. We have studied these cytokines during immune responses to different conjugates in mice. Peptides or proteins were covalently linked to heat-inactivated Brucella abortus (BA) and to keyhole limpet hemocyanin (KLH). BA induced IL-12 and IFNg, whereas KLH elicited IL-4. Consequently the IgG isotype patterns evoked corresponded to the cytokines such that KLH immunization was associated with IgG1>IgG2a ratio, whereas BA elicited IgG2a>IgG1. Similar patterns were observed when BA was administered together with ovalbumin (ova) and alum. In contrast to ova + alum given alone, the combination of BA and ova + alum was associated with IL-12 and IFNg mRNA and protein induction. The isotype patterns observed following ova + alum were high titers of IgG1 and IgE, whereas in the presence of BA, IgG2a predominated and IgG1 and IgE levels were suppressed. BA was also studied for effects on human cells in culture. It had been shown to induce IFNg from human T cells. BA induced IL-12 from human monocytes as shown by increased p40 mRNA and protein. Functional IL-12 was elicited since supernatants from BA-stimulated monocytes caused T cells to secrete IFNg, and this could be blocked by addition of anti-IL-12 antibody. BA also increased expression of B7.1 and B7.2 on human monocytes. These molecules are costimulatory molecules involved in stimulation of T cells. IG preparations were shown to induce IL-1, TNFa and IL-6 from human monocytes. This ability was abrogated by passage of these preparation over polymyxin columns which were shown to remove lipopolysaccharide as determined by limulus amebocyte assays. These studies suggest that the small amounts of LPS contained in IG preparations can elicit cytokines that may explain frequently observed side effects such as fever chills, and headache.