Immunomodulation in Polytrauma and Polymicrobial Sepsis - Where Do We Stand?
Immunomodulation in Polytrauma and Polymicrobial Sepsis - Where Do We Stand?
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DOI：
10.2174/187221311794474892
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发表时间：
2011-01-01
影响因子：
4.2
通讯作者：
Hildebrand, Frank
中科院分区：
文献类型：
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作者：
Neunaber, Claudia;Zeckey, Christian;Hildebrand, Frank
由于治疗策略的改进，多发性创伤患者的死亡率在过去几十年中有所下降。然而，创伤后并发症，如败血症和随后的多器官功能障碍综合征（MODS）仍然是重症监护病房的主要问题。多发性创伤后的临床过程取决于促炎和抗炎免疫反应的平衡或不平衡。促炎反应的优势导致“全身炎症反应综合征”（SIRS），而“代偿性抗炎反应综合征”（汽车）可能导致免疫抑制，增加感染并发症的风险。SIRS和汽车两者在脓毒症和“多器官功能障碍综合征”（MODS）的发展中起关键作用。多发性创伤和脓毒症后宿主反应的性别二态性已经被描述过。在实验和临床研究中，已经发现女性性激素和前体如和rostenediol的保护作用。此外，阻断雄激素受体和抑制二氢睾酮（DHT）的合成显示出对免疫应答的有益作用。除了性激素外，巨噬细胞活化脂肽-2（MALP-2）对Toll样受体（TLR）通路的调节已得到充分描述。此外，硫化氢（H2S）和P物质最近已被发现在炎症动物模型中的促炎作用的重要性。因此，这些药物可能是脓毒症患者新的治疗策略的潜在候选者，以改善多发性创伤患者仍然不令人满意的结果。如果适用，文中提供了每种所述药剂的专利。
Due to improved treatment strategies mortality in multiple trauma patients has been decreased over the last decades. However, posttraumatic complications like sepsis and subsequent multiple organ dysfunction syndrome (MODS) remain a major problem on intensive care units following major trauma. The clinical course after multiple trauma depends on the balance or imbalance of the pro-and anti-inflammatory immune response. The predominance of the pro-inflammatory response leads to the "Systemic Inflammatory Response Syndrome" (SIRS), whereas the "Compensatory Anti-inflammatory Response Syndrome" (CARS) might result in immune suppression with an enhanced risk for infectious complications. Both, SIRS and CARS, play a pivotal role in the development of sepsis and the "Multiple Organ Dysfunction Syndrome" (MODS). A gender dimorphism in the host response after multiple trauma and sepsis has already been described. In experimental as well as clinical studies, a protective effect of female sex hormones and precursors like and rostenediol has been revealed. Moreover, blockade of androgen receptors and the inhibition of dihydrotestosterone (DHT) synthesis were shown to provide beneficial effects on the immune response. Beside sex hormones, modulation of the Toll Like Receptor (TLR) pathway by macrophage-activating lipopeptide-2 (MALP-2) has sufficiently been described. Furthermore, hydrogen sulfide (H2S) and substance P have recently been revealed important for pro-inflammatory action in animal models of inflammation. Thus, these agents might be potential candidates for new treatment strategies in septic patients in order to improve the still unsatisfactory outcome of multiple trauma patients. If applicable, patents of each described agent are provided within the text.