Fukumoto Koji, Nagaoka Isao, Yamataka Atsuyuki, Kobayashi Hiroyuki, Yanai Toshihiro, Kato Yoshifumi, Miyano Takeshi
Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, 113-8421 Bunkyo-ku, Tokyo, Japan.
Pediatr Surg Int. 2005 Jan;21(1):20-4. doi: 10.1007/s00383-004-1256-x.
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.
杀菌肽是一类抗菌肽。人杀菌肽LL-37可抑制内毒素脂多糖（LPS）与CD14阳性细胞的结合，并可改善脓毒症。本研究的目的是观察LL-37对新生大鼠脓毒症的影响。采用腹腔注射（IPI）LPS的方法在乳鼠中建立脓毒症模型。第1组大鼠给予LPS和LL-37，第2组大鼠在给予LPS 2小时后给予LL-37，第3组大鼠只给予LPS。对照组大鼠通过IPI给予等容量的生理盐水。给予LL-37进行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）。在死亡时或IPI后10小时处死时还评估血清C反应蛋白（CRP）。第3组所有大鼠死亡。对于第1组和第2组中接受较低剂量LL-37的大鼠，死亡率降低。第1组中接受较高剂量LL-37的大鼠无死亡发生；然而，第2组中死亡率增加。在第1组中，接受较低剂量LL-37的大鼠OAS和RT最初恶化，然后改善。给予较高剂量LL-37的大鼠在整个研究过程中OAS和RT没有恶化。在第2组中给予较高剂量LL-37的大鼠，OAS和RT与第3组大鼠无显著差异。与第3组相比，第1组CRP显著降低，第2组仅较低剂量时CRP降低。我们得出结论，LL-37可能预防脓毒症，低剂量时可用于治疗脓毒症。然而，高剂量使用LL-37治疗脓毒症时似乎有不良反应。
