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

Abstract

Morbidity and mortality from staphylococcal toxic shock remain high, despite the availability of antibiotics to which the microorganism is sensitive. 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. 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. 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.