1066 DECREASED NEUTROPHIL PRODUCTION AFTER LITHIUM CHALLENGE IN NEWBORN RATS

Abstract

Abnormal host defenses are associated with the neonate's inability to deal with infectious diseases. This study tested the hypothesis that granulocytopoeisis is less efficient in the newborn than the adult. One day old and adult rats were challenged with lithium chloride,an agent which produces neutrophilia by increasing granulocyte production. LiCl(20mg/kg) was administered daily for up to 10 days and the bone marrow and peripheral blood pools measured daily. LiCl did not have a significant effect on the magnitude of the femoral marrow pool in either adults or neonates. The blood neutrophil pool of adults increased by 19% after one day of LiCl treatment. This neutrophilia persisted (260% increase by the day 10). Conversely, the neonatal blood neutrophil pool decreased by 90% after one day of LiCl treatment and remained at that or pretreatment levels throughout the subsequent 10 days(p<0.001 for adults and newborn neutrophil values on days 2-10). Neonates thus were able to maintain a dynamically stable bone marrow pool of neutrophils but were unable to produce a blood neutrophilia in response to LiCl,suggesting a limited responsiveness of hematopoeitic tissues. These data demonstrate another relative defect in the life cycle of the neonatal neutrophil (for example, we have already reported indolent release of neutrophils from the bone marrow pool after endotoxin challenge and inefficient recruitment of phagocytes to focal sites of infection). These abnormal features of neutrophil function may play an important role in the neonate's altered response to infection.