CELLULAR MECHANISMS OF HEMORRHAGED-INDUCED SUPPRESSION

尽管有各种抗菌剂和 严格的预防治疗，感染是主要原因 创伤或烧伤后的发病率和死亡率。一个 抑制的细胞介导的免疫反应似乎主要是 对东道主防守中的损伤负责。我们发现了 “未受创伤”动物的未麻醉出血是 足以导致免疫性抑郁的状态 表现为T细胞增殖减少 有丝分裂原刺激以及IL-2的产生。我们有 进一步发现一种血清免疫抑制因子(SIP)具有 分子量在13,000到23,000之间 淋巴细胞增殖性改变的原因 观察出血后的反应。我们的长期目标是 阐明导致宿主防御受损的事件 在出血和创伤后，并探索可能的临床 SIP的应用，这是本文提出的目标 出血所致改变的特征研究 体内针对特定抗原的免疫反应，并测试 我们的假设是：(1)失血诱导的抑制 免疫应答由SIP介导；(2)SIP抑制 通过激活抑制性T细胞和 从而减少白介素2(IL-2)的产生 辅助性T细胞。具体地说，我们建议：(1)确定影响 出血对发育和效应期的影响 通过检测DTH，了解体内对抗原的免疫反应， 免疫动物的CTL和循环抗体水平 EL4细胞；(2)淋巴细胞亚群(S)测定 对观察到的免疫反应变化负责；(3) 确定是否所有体内免疫反应的改变都会带来 经静脉注射可在大鼠体内复制。 单独给药；(4)阐明作用机制 通过测定其对单核细胞相互作用的影响 和淋巴因子的生产。从这些项目中产生的结果 研究应该使人们更好地理解精神障碍 宿主对出血后感染的防御 和创伤，并提供可能允许 确定创伤患者的方法的发展 特别高的感染风险以及建议独特的 纠正这种情况的治疗方法。

Despite the availability of a variety of antimicrobial agents and rigorous prophylactic therapy, infections are the major cause of morbidity and mortality after traumatic injuries or burns. A depressed cell-mediated immune response appears to be primarily responsible for the impairment in host defense. We have found that unanesthetized hemorrhage in "untraumatized" animals was sufficient by itself to bring about a state of immune depression manifested by a reduced T cell proliferation in response to mitogen stimulation as well as the production of IL-2. We have found further that a serum immunosuppressive factor (SIP) with a molecular weight between 13,000 and 23,000 appears to be responsible for the alterations in lymphocyte proliferative response observed after hemorrhage. With the long term goal of elucidating the events that lead to an impairment in host defense following hemorrhage and trauma and to explore possible clinical applications of SIP, it is the objective of this proposed investigation to characterize the hemorrhage-induced alterations of immune response against specific antigens in vivo, and to test our hypotheses that (1) the hemorrhage-induced suppression of immune response is mediated by SIP and (2) SIP suppresses immune response through activation of suppressor T cells and consequently reduce the production of interleukin 2 (IL-2) by helper T cells. Specifically we propose to: (1) determine effects of hemorrhage on the development as well as the effector phase of immune response against antigens in vivo by measuring DTH, CTL, and levels of circulating antibodies in animals immunized with EL4 cells; (2) determine the subclass(s) of lymphocytes responsible for the observed alterations in immune response; (3) determine if all in vivo alterations of immune response brought about by hemorrhage can be reproduced in rats by i.v. administration of SIP alone; (4) elucidate the mechanism of action of SIP by determining its effects on mononuclear cell interactions and production of lymphokines. Results generated from these studies should lead to a better understanding of the impairment of host defense against infections that occurs following hemorrhage and trauma and provide information which may permit the development of methods to identify trauma patients who are at particularly highly risk of infection as well as suggest unique therapeutic approaches to correct such conditions.