title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Infectious Diseases and Public Health, Department of General Surgery, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Federico
authors.initials: F
authors.lastname: Mocchegiani
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.forename: Alberto
authors.initials: A
authors.lastname: Licci
authors.forename: Jerzy
authors.initials: J
authors.lastname: Łukasiak
authors.forename: Vittorio
authors.initials: V
authors.lastname: Saba
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D015378:Imipenem / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011506:Proteins; C104501:temporin; D015378:Imipenem