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A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats
Koji Fukumoto1, Isao Nagaoka, Atsuyuki Yamataka
1Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, 113-8421 Bunkyo-ku, Tokyo, Japan. kfukumot@hotmail.com
Insights
Human cathelicidin LL-37 shows potential in preventing and treating sepsis in neonatal rats. Lower doses decreased mortality and improved outcomes, but higher doses had adverse effects.
Area of Science:
- Immunology
- Microbiology
- Neonatal Research
Background:
- Cathelicidins are antibacterial peptides with potential therapeutic applications.
- Human cathelicidin LL-37 is known to inhibit endotoxin lipopolysaccharide (LPS) binding, suggesting a role in sepsis.
- Sepsis remains a significant threat, particularly in neonatal populations.
Purpose of the Study:
- To investigate the efficacy of human cathelicidin LL-37 in a neonatal rat model of sepsis.
- To determine the effects of different administration timings and doses of LL-37 on sepsis outcomes.
Main Methods:
- Sepsis was induced in suckling rats via intraperitoneal injection (IPI) of LPS.
- Rats received either LPS with LL-37 concurrently (Group 1), LL-37 2 hours after LPS (Group 2), or LPS alone (Group 3).
- Overall assessment score (OAS), rectal temperature (RT), and serum C-reactive protein (CRP) were monitored. Mortality rates were recorded.
Main Results:
- All rats receiving LPS alone (Group 3) died.
- LL-37 administration, particularly at higher doses concurrently with LPS (Group 1), significantly reduced mortality and improved OAS and RT.
- Lower doses of LL-37 in Group 2 also decreased mortality, but higher doses in Group 2 showed no benefit compared to Group 3. CRP levels were reduced in Group 1.
Conclusions:
- Human cathelicidin LL-37 demonstrates potential as a preventative and therapeutic agent for sepsis in neonatal rats.
- Lower doses of LL-37 appear beneficial for sepsis treatment, while higher doses may have adverse effects.
- Timing and dosage are critical factors for the efficacy of LL-37 in managing sepsis.
Abstract:
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.
