Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats
Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats
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DOI：
10.1007/s00383-004-1256-x
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发表时间：
2005-01-01
影响因子：
1.8
通讯作者：
Miyano, T
中科院分区：
文献类型：
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作者：
Fukumoto, K;Nagaoka, I;Miyano, T
Cathelicidins是一类抗菌肽。人cathelicidin LL-37抑制内毒素脂多糖（LPS）与CD 14阳性细胞的结合，并可改善脓毒症。本研究旨在观察LL-37对新生大鼠脓毒症的治疗作用。腹腔内注射（IPI）LPS在乳鼠中产生脓毒症。第1组大鼠给予含LL-37的LPS，第2组大鼠在LPS后2 h给予LL-37，第3组大鼠给予不含LL-37的LPS。对照组给予等容生理盐水。将给予LL-37 IPI的大鼠分为7个亚组。IPI后，每小时评估一次总体评估评分（OAS）和直肠温度（RT）。血清C-反应蛋白（CRP）也进行了评估死亡或处死后10小时IPI。第3组大鼠全部死亡。对于在组1和组2中接受较低剂量的LL-37的大鼠，死亡率降低。在第1组中接受较高剂量LL-37的患者中没有发生死亡;然而，在第2组中死亡率增加。在第1组中，对于接受较低剂量LL-37的那些，OAS和RT最初恶化，然后改善。在给予较高剂量LL-37的大鼠中，OAS和RT在整个研究期间没有恶化。在给予较高剂量LL-37的第2组大鼠中，OAS和RT与第3组大鼠无显著差异。与第3组相比，第1组的CRP显著降低，第2组仅在较低剂量下降低。我们的结论是，LL-37可以预防脓毒症，并在低剂量治疗脓毒症是有用的。然而，LL-37在以更高剂量用于治疗脓毒症时似乎具有副作用。
Cathelicidins are a family of antibacterial peptides. Human cathelicidin LL-37 inhibits the binding of endotoxin lipopolysaccharide (LPS) to CD14-positive cells and could ameliorate sepsis. The aim of this study was to observe the effect of LL-37 on sepsis in neonatal rats. Intraperitoneal injection (IPI) of LPS was used to create sepsis in suckling rats. Group 1 rats were given LPS with LL-37, group 2 rats were given LL-37 2 h after LPS, and group 3 rats were given LPS without LL-37. Control group rats were given isovolemic normal saline by IPI. Rats given LL-37 IPI were divided into seven subgroups. Following IPI, an overall assessment score (OAS) and rectal temperature (RT) were assessed hourly. Serum C-reactive protein (CRP) was also assessed at death or at sacrifice 10 h after IPI. All rats in group 3 died. For rats receiving lower doses of LL-37 in groups 1 and 2, mortality was decreased. No deaths occurred among those receiving higher doses of LL-37 in group 1; however, mortality increased in group 2. In group 1, OAS and RT deteriorated initially for those receiving lower doses of LL-37, then improved. OAS and RT did not deteriorate throughout the study in rats given higher doses of LL-37. In group 2 rats given higher doses of LL-37, OAS and RT were not significantly different from rats in group 3. CRP was significantly decreased in group 1 compared with group 3, and decreased in group 2 for lower doses only. We conclude that LL-37 may prevent sepsis and be useful in lower doses for treating sepsis. However, LL-37 appears to have adverse effects when used at higher doses for treating sepsis.