EFFECT OF CHRONIC ERYTHROPOIETIN ADMINISTRATION ON PLASMA IRON IN NEWBORN LAMBS

Erythropoietin, the primary stimulator of erythropoiesis, represents a n important potential therapy for the anemia of prematurity. Enhanceme nt of the therapeutic benefit of recombinant human erythropoietin (rhE p) in very-low-birth-weight infants will require a better understandin g of rhEp's pharmacodynamic effects including its interaction with iro n in stimulating erythropoiesis. The purpose of this study was to dete rmine the effects of chronic rhEp administration on plasma iron levels and hematopoiesis using a twin lamb model. Nine pairs of twin lambs i n which one twin was randomized to receive rhEp, and the other saline, were studied during a 1-week baseline and a subsequent 4- to 5-week t reatment period. The effects of therapy on plasma iron levels and eryt hropoiesis were measured by integrating the areas under the concentrat ion-time curves (AUC) of the study variables. During the rhEp treatmen t period, significantly greater negative daily AUCs were observed in t he rhEp-treated lambs for plasma iron concentration (p = 0.0008), whil e significantly greater positive daily AUCs were observed for hemoglob in concentration (p = 0.04) and reticulocyte count (p = 0.02). In the rhEp-treated group, pretreatment iron concentrations were directly ass ociated with the magnitude of the iron response during treatment such that the greater the pretreatment iron, the greater the daily AUC belo w the plasma iron concentration-time plot (r = -0.66, p = 0.05). For t he placebo-treated group, this association tended toward, but did not achieve, statistical significance (r = -0.52, p = n.s.). These observa tions suggest that treatment of rapidly growing newborn lambs with rhE p results in increased iron utilization due to increased erythropoiesi s and depends on iron status at the initiation of rhEp treatment. Use of the term neonatal lamb model offers advantages over studiesv in hum an infants for more detailed or invasive examinations of the interacti on of iron and rhEp treatment.