TYPE OF INFECTION ON EFFECTS OF ENDOTOXIN ANALOG

到目前为止，脓毒症患者使用抗炎药的临床经验一直令人失望。我们发现，感染的部位、类型和严重程度等几个因素对许多这些病原体都有重要的影响。开发受这些因素影响最小的新药物，将增加这种治疗方法的有用性。内毒素在脓毒症损伤中的作用尚不清楚。在许多情况下，它很可能会产生有害影响。在脓毒症中，靶向内毒素而不是宿主介体可能是一个更普遍有用的目标。到目前为止，针对内毒素的抗体在脓毒症中几乎没有效果，因为分子中有毒的脂肪部分可能很难靶向。另一种中和内毒素的方法是使用类似分子，这种分子竞争性地抑制内毒素发出的细胞信号。我们目前正在进行一系列研究，调查感染部位、严重程度和类型对内毒素竞争性抑制物的影响。

Clinical experience with anti-inflammatory agents in patients with sepsis has been disappointing to date. We have found that several factors such as the site, type, and severity of infection have important influences on many of these agents. Developing new agents which are impacted minimally by such factors, will increase the usefulness of this therapeutic approach. The role of endotoxin in the injury of sepsis is unclear. It is likely that under many circumstances it produces harmful effects. Targeting endotoxin rather than host mediators may be a more generally useful goal in sepsis. Antibodies against endotoxin have had little effect to date in sepsis because the toxic lipid portion of the molecule may be difficult to target. An alternative approach to neutralizing endotoxin uses analogue molecules which competitively inhibit cell signaling by endotoxin. We are currently performing a series of studies investigating the influence of site, severity, and type of infection on a competitive inhibitor of endotoxin.