IMMUNOMODULATION IN SURGICAL/TRAUMA/BURN PATIENTS

细胞免疫缺陷与炎症和抗体 反应无疑会导致患者感染和死亡。 正在接受手术，并遭受严重创伤和烧伤的人。那里有 在控制免疫反应和预防方面进展有限 这种损伤后的免疫性抑郁。在我们之前的研究中，我们有 记录了烧伤后小鼠的特异性免疫缺陷，并 在骨骼创伤之后；我们还证明了特定的 药物治疗可以改善这类动物的免疫功能 损伤(迟发性超敏反应，脾淋巴细胞“辅助/抑制” 比率和对败血症挑战的抵抗力)。先导性临床研究已经 研究表明，一些相同的药物似乎可以防止心脏发生变化 大手术后循环淋巴细胞亚群。 该项目将确定特定的药物治疗是否可以改善 烧伤后动物和患者的额外免疫功能 在烧伤、创伤和重大外科手术后。这些药物 将使用我们在以前的实验中展示的那些 提高烧伤(小鼠)、骨骼创伤(小鼠)和严重烧伤后的免疫力 外科手术(人类)。我们怀疑这些药物，我们称之为 免疫调节药物在本提案中，通过阻断发挥其作用 术后抑制性淋巴细胞群的活化或增殖 受伤。实验旨在提供以下信息：1) 测定组胺-2受体拮抗剂前列腺素的能力 阻滞剂、环磷酰胺和硝酸铈影响多重免疫 烧伤小鼠的功能，使用不同的药物剂量；2)确定 西咪替丁(组胺-2阻滞剂)和布洛芬(A)的作用 前列腺素阻滞剂)对大手术后免疫功能的影响 人体程序，使用多项免疫功能测量；3) 确定相同药物对重大疾病后相似免疫功能的影响 人类的非烧伤创伤，将损伤的严重程度与特定的 免疫反应；4)确定相同药物对相似免疫的影响 烧伤后的功能，将烧伤的程度与 特定的免疫反应。

Defects in cell-mediated immunity and the inflammatory and antibody responses undoubtedly contribute to infections and mortality in patients undergoing surgery and who suffer major trauma and burn injury. There has been limited progress in controlling the immune responses and preventing immune depression after such injuries. In our previous studies we have documented specific immune deficits in mice following burn injury and following skeletal trauma; we have also demonstrated that specific pharmacologic therapy can improve immune functions in such animals after injury (delayed hypersensitivity, splenic lymphocyte "helper/suppressor" ratios, and resistance to septic challenge). Pilot clinical studies have shown that some of the same drugs appear to prevent alterations in circulating lymphocyte subpopulations after major surgical procedures. This project will determine if specific pharmacologic therapy can improve additional immune functions in animals after burn injury and in patients after burn injury, trauma and major surgical procedures. The drugs utilized will be those which we have shown in previous experiments to improve immunity following burns (mice), skeletal trauma (mice) and major surgery (humans). We suspect that these drugs, which we have termed immunmodulating drugs in this proposal, exert their effects by blocking activation or proliferation of suppressor lymphocyte populations after injury. Experiments are designed to provide the following information: 1) Determine the ability of histamine-2 receptor antagonists, prostaglandin blockers, cyclophosphamide, and cerium nitrate to affect multiple immune functions in burned mice, using varying drug dosages; 2) Determine the ability of cimetidine (a histamine-2 blocker) and ibuprofen (a prostaglandin blocker) to affect immune functions after major surgical procedures in humans, using multiple measures of immune function; 3) Determine effects of the same drugs on similar immune functions after major non-burn trauma in humans, correlating severity of injury with specific immune responses; 4) Determine effects of the same drugs on similar immune functions after burn injury, correlating the magnitude of burn injury with specific immune responses.