HIGH IN-VITRO ENDOTOXIN RESPONSIVENESS OF MACROPHAGES FROM AN ENDOTOXIN-RESISTANT WILD RODENT SPECIES, SIGMODON HISPIDUS

It has been reported that macrophages primarily mediate endotoxin shoc k and cell death by synthesizing and releasing cytokines, largely tumo r necrosis factor (TNF) and interleukin-1 (IL-1). However, macrophages from some laboratory mouse strains such as C3h/HeN are unresponsive t o endotoxin both in vivo and in vitro. We found members of a wild rode nt species, Sigmodon hispidus, to also be extremely resistant to bacte rial endotoxin challenge. intravenous administration of up to 100,000 mu g/kg body mass of Escherichia coli O26:B6 endotoxin did not cause l ethality in adult S. hispidus. In contrast to the endotoxin-resistant mouse strain, peritoneal macrophages derived from S. hispidus were res ponsive to in vitro endotoxin challenge as measured by high levels of TNF and IL-1 activity in supernatants of macrophage cultures. Thus, in vitro macrophage responsiveness to endotoxin does not always indicate high host sensitivity to endotoxin challenge.