Ascorbic acid modulates in vitro the function of macrophages from mice with endotoxic shock

The toxic effects of oxygen radicals produced by immune cells can be contro lled to certain degree by endogenous antioxidants because of their scavenge r action. This control is specially important in a type of immune cell, i.e ., the phagocyte, which produces oxygen-free radicals and uses antioxidants in order to support its functions. Antioxidants, such as ascorbic acid (AA ), are free radical scavengers and improve the immune response. in the path ogenesis of endotoxic shock, a disease with high mortality caused by Gram-n egative bacterial endotoxin, the reactive oxygen species (ROS) produced by phagocytes have been implicated. In a previous study, we observed in perito neal macrophages from BALB/c mice suffering lethal endotoxic shock caused b y intraperitoneal (i.p.) injection of Escherichia coli lipopolysaccharide ( LPS; 100 mg/kg) a high production of superoxide anion. Therefore, in the pr esent work, we have studied the in vitro effect of AA, at different concent rations (0.001, 0.01, 0.1, 1 and 2.5 mM), on the various steps of the phago cytic process, i.e., adherence to substrate, chemotaxis, ingestion of parti cles and superoxide anion production of murine peritoneal macrophages obtai ned from BALB/c mice with that of endotoxic shock, at 2, 4, 12 and 24 h aft er LPS injection. The increased adherence, ingestion and superoxide anion p roduction by macrophages from animals with endotoxic shock were lower in th e presence of AA, reaching similar values to those of the control animals. The most effective AA concentration in cells from mice with endotoxic shock was 0.01 mM. These data suggest that AA can regulate the phagocytic proces s in endotoxic shock, principally decreasing free radical production and th us it could reduce endotoxic shock severity. (C) 2000 Elsevier Science B.V. All rights reserved.