Evidence that endotoxin is the cyclic 3':5'-GMP--promoting factor in erythropoietin preparations

Since Ep preparations are contaminated with endotoxin, the possibility that the latter might be the factor in crude Ep which increases cGMP levels in rat fetal liver cells was examined. Endotoxin produced a striking elevation of cGMP in rat fetal liver cells without affecting cAMP levels or heme synthesis. Absorption with Limulus lysate of more than 99% of the endotoxin in a crude Ep preparation caused a parallel decrease in the cGMP-promoting activity without reduction of heme synthetic potency. It is concluded that endotoxin is the component of crude Ep which increases cGMP levels in rat fetal liver. The precise role of elevated cGMP in the action of endotoxin on cells and the universality of this effect remain to be determined.