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 shock and cell death by synthesizing and releasing cytokines, largely tumor necrosis factor (TNF) and interleukin-1 (IL-1). However, macrophages from some laboratory mouse strains such as C3h/HeN are unresponsive to endotoxin both in vivo and in vitro. We found members of a wild rodent species, Sigmodon hispidus, to also be extremely resistant to bacterial endotoxin challenge. Intravenous administration of up to 100,000 micrograms/kg body mass of Escherichia coli O26:B6 endotoxin did not cause lethality in adult S. hispidus. In contrast to the endotoxin-resistant mouse strain, peritoneal macrophages derived from S. hispidus were responsive 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.