Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis.
To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.
Matsumoto
T
T
Department of Microbiology, Toho University School of Medicine, Omori-Nishi, Ota-ku, Tokyo, Japan.
Tateda
K
K
Miyazaki
S
S
Furuya
N
N
Ohno
A
A
Ishii
Y
Y
Hirakata
Y
Y
Yamaguchi
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016470:Bacteremia / Q000097:blood / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D015169:Colony Count, Microbial; D003520:Cyclophosphamide / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007422:Intestines / Q000382:microbiology; D051379:Mice; D011552:Pseudomonas Infections / Q000097:blood / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D011994:Recombinant Proteins / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide