The efficacy of a monoclonal antibody directed against tumor necrosis factor in protecting neutropenic rats from lethal infection with Pseudomonas aeruginosa

A monoclonal antibody directed against murine tumor necrosis factor-a (TNF) was studied in a neutropenic rat model to determine its efficacy in protecting animals from lethal infection with Pseudomonas aeruginosa. Anti-TNF monoclonal antibody at a dose of 20 mg/kg given in-travenously at 0 and 120 h resulted in a 53 % survival rate (8/15) compared with no survival in control animals (0/15) (P <.(05). The combination of anti-TNF monoclonal antibody and oral ciprofloxacin at a suboptimal dose of 2.5 mg/kg/day resulted in a 100 % survival rate in neutro-penic animals (16/16), while ciprofloxacin alone produced only, a 67 % survival rate (10/15) during the 7-day period of neutropenia (P <.05). Thus anti-TNF monoclonal antibody alone or in addition to antimicrobial agents improved survival in neutropenic animals after infection with P. oeruginosa. The mortality rate associated with gram-negative septice-mia in neutropenic patients remains unacceptably high de-spite the availabilityof a wide variety of potent broad-spectrum antimicrobial agents [1,2]. Additional therapeutic strategies have been sought to decrease the mortality rate associate