Quantitative and qualitative aspects of steady state erythropoiesis induced in protein-starved rats by long-term erythropoietin injection.

By KENJUIO ITO AND KURT R. REISSMANN T HE ABSENCE of protein from the food of rats results within a few (lays in a depression of red cell formation, and the latter proceeds during the first 4 dietary weeks at approximately one-tenth of its normal rate.1 If protein starvation is continued, a gradual recovery of erythropoiesis is noted, and the red cell mass tends to stabilize around one-half of its normal value. Evidence has been presented2’ in support of a diminished erythropoietin formation as the cause of the erythropoietic depression, and experiments employing shortterm injection of erythropoietin have failed to detect any rate-limiting effect of the protein deficiency on red cell synthesis per se. The present study attempts to determine whether rabbit erythropoietin, injected daily over a period of 1 month, can induce in protein-starved rats a steady state erythropoiesis which is quantitatively and qualitatively equal to that in normal rats. Such demonstration would lend further support to the dependency of normal erythropoiesis on erythropoietin. It would also prove that erythropoietin, extracted from plasma of anemic rabbits, provides complete substitution for lacking endogenous erythropoietin in the rat, and would permit an estimate of erythropoietin requirements during normal steady states. Accordingly, a daily dose of erythropoietin was selected which sustained reticulocytes in the protein-starved rats at levels equal to those in normal controls. The quantity of red cells formed in these animals was assessed by comparing their red cell mass at the end of a period of 32 days with that in normal controls or in untreated protein-starved rats. As it will be shown, nearly 40 per cent of the cells present were formed in response to the injected rabbit erythropoietin. The quality of these cells could thus h assessed with a high degree of confidence, because abnormalities in regard to physical properties or longevity of such a large fraction of the total cell population should he readily detectable.