title: Modulation of inflammatory response in a cirrhotic rat model with induced bacterial peritonitis.
abstract: Bacterial peritonitis is a severe complication in patients with cirrhosis and ascites and despite antibiotic treatment, the inflammatory response to infection may induce renal dysfunction leading to death. This investigation evaluated the effect of TNF-α blockade on the inflammatory response and mortality in cirrhotic rats with induced bacterial peritonitis treated or not with antibiotics. Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis were treated with an intraperitoneal injection of 10(9) CFU of Escherichia coli diluted in 20 mL of sterile water to induce bacterial peritonitis and randomized to receive subcutaneously-administered placebo, ceftriaxone, anti-TNF-α mAb and ceftriaxone, or anti-TNF-α mAb alone. No differences were observed between groups at baseline in respect to renal function, liver hepatic tests, serum levels of nitrite/nitrate and TNF-α. Treatment with ceftriaxone reduced mortality (73.3%) but differences did not reach statistical significance as compared to placebo. Mortality in rats treated with ceftriaxone and anti-TNF-α mAb was significantly lower than in animals receiving placebo (53% vs. 100%, p<0.01). Serum TNF-α decreased significantly in surviving rats treated with ceftriaxone plus anti-TNF-α mAb but not in treated with antibiotics alone. Additional studies including more animals are required to assess if the association of antibiotic therapy and TNF-α blockade might be a possible approach to reduce mortality in cirrhotic patients with bacterial peritonitis.
authors.affiliation: Liver Section, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Sánchez
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
authors.forename: Germán
authors.initials: G
authors.lastname: Soriano
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mirelis
authors.forename: Francesc J
authors.initials: FJ
authors.lastname: Sancho
authors.forename: José Manuel
authors.initials: JM
authors.lastname: González-Navajas
authors.forename: Carlos
authors.initials: C
authors.lastname: Muñoz
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Song
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Mateo
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.forename: Carlos
authors.initials: C
authors.lastname: Guarner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002443:Ceftriaxone / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D007118:Immunoassay; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000150:complications*; D008297:Male; D010538:Peritonitis / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D002443:Ceftriaxone; D002251:Carbon Tetrachloride