Modulation of Inflammatory Response in a Cirrhotic Rat Model with Induced Bacterial Peritonitis

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-alpha 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-alpha mAb and ceftriaxone, or anti-TNF-alpha 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-alpha. 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-alpha mAb was significantly lower than in animals receiving placebo (53% vs. 100%, p<0.01). Serum TNF-alpha decreased significantly in surviving rats treated with ceftriaxone plus anti-TNF-alpha 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-alpha blockade might be a possible approach to reduce mortality in cirrhotic patients with bacterial peritonitis.