Abstract: We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone.

Keywords: synergism, tissue damage, bacterial toxin, bacteriolysis, cationic proteins, sepsis




中文翻译：

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病原体、垂死的宿主细胞和中性粒细胞释放的促炎剂协同作用破坏宿主组织：一个可行的假设。

摘要：我们假设许多感染、炎症和炎症后事件造成的广泛细胞和组织损伤是入侵微生物、宿主中性粒细胞以及病巢中死亡和垂死细胞之间协同作用的结果。微生物毒素和其他代谢物，以及从大量聚集到感染部位的活化中性粒细胞释放的大量促炎剂，以及从活化的多形核中性粒细胞 (PMN) 和坏死的中性粒细胞释放的高水平阳离子组蛋白、其他阳离子肽、蛋白酶和 Th1 细胞因子组织可能协同作用（协同作用），导致细胞死亡和组织破坏。在这些复杂的病变中，许多潜在的促炎部分之间存在多种、不同的相互作用。此类感染常见于组织暴露于环境的皮肤和呼吸消化道，但也可以发生在任何组织中。通常，组织破坏性感染是由 A 族链球菌、肺炎球菌、金黄色葡萄球菌、脑膜炎球菌、大肠杆菌和志贺氏菌引起的，但有时也会看到许多其他微生物种类。所有这些微生物制剂的特点是能够招募大量中性粒细胞。鉴于疾病过程的复杂性，有人建议，为了治疗这些多因素疾病，抗炎药与非溶菌抗生素的“混合物”以及抵消阳离子部分关键毒性作用的措施可能会更有效而不是仅基于攻击细菌的策略。

关键词：协同作用，组织损伤，细菌毒素，溶菌，阳离子蛋白，败血症