Changes in the Superoxide Production and Other Macrophage Functions Could Be Related to the Mortality of Mice with Endotoxin-Induced Oxidative Stress

V. M. VÍCTOR, M. DE LA FUENTE

Received January 10, 2002
Accepted May 22, 2002

Summary
Free radicals and proinflammatory cytokines from phagocytes have been implicated in the pathogenesis of endotoxic shock, a disease with high mortality caused by Gram-negative bacterial endotoxin. In the present study, male BALB/c and Swiss mice received intraperitoneally lipopolysaccharide (LPS) at 100 mg/kg and 150 mg/kg, respectively, that led to a lethal endotoxic shock (100 % of mortality before 30 h). Swiss mice injected with 100 mg/kg, that did not show lethal endotoxic shock, were also studied. Peritoneal macrophages were obtained from animals at 2, 4, 12 or 24 h after injection of LPS or saline (control) solutions. Superoxide anion and tumor necrosis factor (TNFα) production were determined in these cells as well as other functions such as adherence capacity, chemotaxis and phagocytosis. The increase in superoxide anion production after endotoxin injection was higher in cells from mice with lethal shock than in those with non-lethal shock. However, the enhancement of TNFα production was similar in all cases, although in Swiss mice the highest levels of TNFα were observed at 1.5 h after endotoxin injection, while in BALB/c mice they occurred at 2 h after LPS injection. This oxidative stress was also revealed by the other functions analyzed, since adherence to substrate and phagocytosis were stimulated and chemotaxis was decreased after endotoxin injection as compared to controls, the differences being even more significant in animals with lethal shock. These data suggest that these changes, mainly the increased production of free radicals even more than the TNFα release, could be involved in mouse mortality caused by LPS.

Key words
Immune function • Macrophage • Mice • Oxidative Stress • Superoxide anion

Reprint requests
Dr. Mónica De la Fuente, Departamento de Biología Animal II (Fisiología Animal). Facultad de Ciencias Biológicas. Universidad Complutense. Av. Complutense s/n, 28040 Madrid, Spain. Fax: +34-91-3944935, e-mail: mondelaf@bio.ucm.es