IFN-gamma involvement in the severity of gram-negative infections in mice.
The role of IFN-gamma in the regulation of inflammation leading to gram-negative septic shock is still poorly understood. IFN-gamma blockade has been shown to improve the survival of animals challenged with i.v. bolus injections of LPS and gram-negative bacteria. We have investigated a model of focal Escherichia coli infection leading to peritonitis and septic shock. Mice were challenged i.p. with an inoculum near the LD50. The addition of rIFN-gamma together with bacteria increased the mortality and the level of blood TNF-alpha and IL-6. Conversely blockade of IFN-gamma with a neutralizing mAb significantly improved the survival of the mice. This beneficial effect was not associated with a stringent decrease in blood bacterial counts and TNF-alpha and IL-6 levels in survivors. In this model, the protective effect of anti-IFN-gamma mAb contrasted with the ineffectiveness of a neutralizing anti-TNF-alpha mAb. These findings suggest that overproduction of IFN-gamma might have a more detrimental role than overproduction of TNF-alpha during focal gram-negative infections.
Kohler
J
J
Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Heumann
D
D
Garotta
G
G
LeRoy
D
D
Bailat
S
S
Barras
C
C
Baumgartner
J D
JD
Glauser
M P
MP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D005260:Female; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D010538:Peritonitis / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma