Temporin A alone and in combination with imipenem reduces lethality in a mouse model of staphylococcal sepsis.

Abstract

BACKGROUND: Morbidity and mortality from staphylococcal toxic shock remain high, despite the availability of antibiotics to which the microorganism is sensitive. METHODS: In in vitro experiments, the ability of temporin A to inhibit lipoteichoic acid-induced production of tumor necrosis factor (TNF)- alpha and nitric oxide (NO) was determined. Also, mouse models of staphylococcal sepsis were used to evaluate the efficacy of temporin A alone and in combination with imipenem. BALB/c mice were injected intravenously with live Staphylococcus aureus or heat-killed cells and then received either isotonic sodium chloride solution, 2 mg/kg temporin A, 7 mg/kg imipenem, or 2 mg/kg temporin A in combination with 7 mg/kg imipenem immediately and 6 h after challenge. The main outcome measures were lethality rates, plasma bacterial counts, and plasma TNF- alpha and interleukin (IL)-6 levels. RESULTS: The in vitro experiments showed that temporin A did not cause TNF- alpha or NO release. In the in vivo experiments with live bacteria, both compounds reduced lethality rates and bacterial growth. Imipenem exhibited the highest efficacy. The combination-treated group had significantly lower bacterial counts than did the singly-treated groups and the lowest lethality rates. In the experiments with heat-killed cells, only temporin A demonstrated significant efficacy with respect to lethality and reduction of plasma TNF- alpha and IL-6 levels. DISCUSSION: This study shows that temporin A can reduce the stimulatory effects of bacterial cell components and suggests that it may be beneficial in the treatment of severe staphylococcal sepsis.