DECREASED LACTATE IN ENDOTOXIN-RESISTANT MICE UNDERGOING HEMORRHAGE IS INDEPENDENT OF TUMOR-NECROSIS-FACTOR AVAILABILITY

Although C3H/HeJ mice, characterized by a genetic deficiency in macrop hage cytokine release in response to endotoxin, have been studied exte nsively to gain insight into the possible role of various cytokines in sepsis, few past studies have examined the physiologic response to he morrhagic shock in this ''enodotoxin-resistant'' strain. We utilized a fixed-volume model of hemorrhagic shock and two different levels of h emorrhage severity (50 and 67% blood volume) to compare C3H/HeJ mice t o normal C3H/HeN mice. An additional group of endotoxin-sensitive C3H/ HeN mice were treated with 2.5 mg/kg of anti-tumor necrosis factor (TN F) antibody to define the possible role of TNF in shock physiology. He matocrit, circulating neutrophils, and plasma glucose and lactate conc entrations were measured following hemorrhage. TNF increased significa ntly following hemorrhage in normal mice but did not increase in C3H/H eJ mice or in C3H/HeN mice treated with anti-TNF antibody. No differen ce between groups was identified in hematocrit, circulating neutrophil s, or glucose. Whereas plasma lactate increased significantly by 30 mi n in all groups, lactate returned to baseline levels in C3H/HeJ mice a t 60 min, but remained persistently elevated in C3H/HeN mice and in C3 H/HeN mice treated with anti-TNF antibody. The data demonstrate attenu ated lactate accumulation in C3H/HeJ mice following hemorrhage. Inhibi tion of circulating TNF activity with anti-TNF antibody failed to repr oduce this late decrease in plasma lactate in normal mice. The data su ggest that macrophage products other than TNF known to be deficient in C3H/HeJ mice contribute to anaerobic metabolism in hemorrhagic shock. (C) 1994 Academic Press, Inc.