Antibiotic treatment in a murine model of sepsis: impact on cytokines and endotoxin release.
Experimental and clinical studies in sepsis indicate that antibiotic therapy may induce the release of endotoxin (LPS) from the outer membrane of gram-negative bacteria and therefore may affect the physiologic response and survival. The aim of this study was to evaluate if antibiotics commonly used to treat secondary peritonitis are capable of changing survival rates, proinflammatory and anti-inflammatory cytokine concentrations, and the release of endotoxin in a murine model of sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in Swiss mice using an 18-gauge needle. The animals received injections of saline solution or imipenem or a combination of ciprofloxacin plus clindamycin every 8 h for 3 days. Antibiotic treatment induced an increase in survival rate and decreased plasma and peritoneal fluid levels of TNF-alpha and IL-6 at 6 and 24 h after CLP as compared with saline-treated animals. Antibiotic-treated animals also showed an early (6 h) decrease and a late (24 h) increase in IL-10 concentration in the peritoneal fluid. LPS concentrations were elevated in all groups, but imipenem-treated animals showed higher levels (2.2 EU/mL) than ciprofloxacin plus clindamycin (1.3 EU/mL) and saline-treated (1.5 EU/mL) groups. We conclude that antibiotic-induced endotoxin release is not a major determinant in the inflammatory response and prognosis in murine models of sepsis.
Vianna
Rosa C S
RC
Intensive Care Unit, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.
Gomes
Rachel N
RN
Bozza
Fernando A
FA
Amâncio
Rodrigo T
RT
Bozza
Patrícia T
PT
David
Cid M N
CM
Castro-Faria-Neto
Hugo C
HC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use; D002432:Cecum / Q000293:injuries / Q000473:pathology; D002939:Ciprofloxacin / Q000627:therapeutic use; D002981:Clindamycin / Q000627:therapeutic use; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006090:Gram-Negative Bacteria / Q000378:metabolism; D015378:Imipenem / Q000627:therapeutic use; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D018805:Sepsis / Q000188:drug therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002981:Clindamycin; D002939:Ciprofloxacin; D015378:Imipenem