Unit of Experimental Medicine, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium.
Department of Pathology, University of Medicine 1, Yangon 11131, Myanmar.
Int J Mol Sci. 2023 May 16;24(10):8851. doi: 10.3390/ijms24108851.
Sepsis is a common disease in sub-Saharan Africa and Asia, where malaria is also prevalent. To determine whether infection might enhance susceptibility to endotoxin shock, we used a mouse model of lipopolysaccharide (LPS) administration. Our results indicated that infection in mice strongly enhanced the susceptibility of the host to develop endotoxin shock. This increased susceptibility to endotoxin shock was correlated with a synergistic effect of and LPS on the secretion of Tumor Necrosis Factor (TNF). TNF contributed mostly to lethality after the dual challenge since neutralization with an anti-TNF antibody provided protection from death. infection also induced an enhancement of the serum levels of LPS soluble ligands, sCD14 and Lipopolysaccharide Binding Protein. In this regard, our data confirm that infection can profoundly modify responses to secondary bacteria challenges, resulting in dysregulated cytokine expression and pathological effects. If confirmed in humans, LPS soluble receptors might serve as markers of susceptibility to septic shock.
疟疾在撒哈拉以南非洲和亚洲地区很常见，而这些地区也是败血症的高发地区。为了确定感染是否会增加内毒素休克的易感性，我们使用了脂多糖（LPS）给药的小鼠模型。我们的结果表明，疟疾感染强烈增强了宿主对内毒素休克的易感性。这种对内毒素休克易感性的增加与疟原虫和 LPS 对肿瘤坏死因子（TNF）分泌的协同作用相关。TNF 在双重挑战后导致了大部分的致死性，因为抗 TNF 抗体的中和作用提供了对死亡的保护。疟原虫感染还诱导了 LPS 可溶性配体、sCD14 和脂多糖结合蛋白的血清水平升高。在这方面，我们的数据证实疟原虫感染可以深刻地改变对二次细菌挑战的反应，导致细胞因子表达和病理效应失调。如果在人类中得到证实，LPS 可溶性受体可能作为脓毒症休克易感性的标志物。
