Sepsis Research Today is a free monthly online journal that collates and summarizes the latest research about Sepsis, including details on septicemia, diagnosis, symptoms, treatment.

LL-37 protects rats against lethal sepsis caused by gram-negative bacteria.

Cirioni O, Giacometti A, Ghiselli R, Bergnach C, Orlando F, Silvestri C, Mocchegiani F, Licci A, Skerlavaj B, Rocchi M, Saba V, Zanetti M, Scalise G

Università Politecnica delle Marche, Clinica Malattie Infettive, c/o Ospedale Regionale, Via Conca 71, 60020 Torrette, Ancona, Italy.

We investigated the efficacy of LL-37, the C-terminal part of the only cathelicidin in humans identified to date (termed human cationic antimicrobial protein), in three experimental rat models of gram-negative sepsis. Adult male Wistar rats (i) were given an intraperitoneal injection of 1 mg Escherichia coli 0111:B4 LPS, (ii) were given 2 x 10(10) CFU of Escherichia coli ATCC 25922, or (iii) had intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 1-mg/kg LL-37, 1-mg/kg polymyxin B, 20-mg/kg imipenem, or 60-mg/kg piperacillin. Lethality; growth of bacteria in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; and endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma were evaluated. All compounds reduced lethality compared to levels in controls. Endotoxin and TNF-alpha plasma levels were significantly higher in conventional antibiotic-treated rats than in LL-37- and polymyxin B-treated animals. All drugs tested significantly reduced bacterial growth compared to saline treatment. No statistically significant differences between LL-37 and polymyxin B were noted for antimicrobial and antiendotoxin activities. LL-37 and imipenem proved to be the most effective treatments in reducing all variables measured. Due to its multifunctional properties, LL-37 may become an important future consideration for the treatment of sepsis.

Published 27 April 2006 in Antimicrob Agents Chemother, 50(5): 1672-9.
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