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-alpha (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 intravenously at 0 and 120 h resulted in a 53% survival rate (8/15) compared with no survival in control animals (0/15) (P less than .005). 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 neutropenic animals (16/16), while ciprofloxacin alone produced only a 67% survival rate (10/15) during the 7-day period of neutropenia (P less than .05). Thus anti-TNF monoclonal antibody alone or in addition to antimicrobial agents improved survival in neutropenic animals after infection with P. aeruginosa.
Opal
S M
SM
Infectious Disease Section, Memorial Hospital of Rhode Island, Pawtucket 02860.
Cross
A S
AS
Kelly
N M
NM
Sadoff
J C
JC
Bodmer
M W
MW
Palardy
J E
JE
Victor
G H
GH
D000380:Agranulocytosis / Q000150:complications*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000097:blood / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D007275:Injections, Intravenous; D009503:Neutropenia / Q000150:complications*; D011552:Pseudomonas Infections / Q000150:complications / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D002939:Ciprofloxacin