Comparative Study of Escherichia coli Endotoxin,Hydrocortisone and Beljanski Leukocyte Restorer Activity in Cyclophosphamide-Treated Rabbits 1

Abstract

The leukopoietic activity of Beljanski leukocyte restorer(s) (BLR(s)) (RNA-fragments obtained from Escherichia coli rRNA), E. coli endotoxin, and hydrocortisone administered iv was compared in rabbits treated daily with high doses of cyclophosphamide (CP), a drug which decreases the circulating leukocyte count. Results showed that endotoxin and hydrocortisone responses, characterized essentially by granulocytosis, occurred 3–24 hr following drug injection and disappeared thereafter. Maximal BLR leukocytosis occurred at the 48th hr and remained, even during daily CP administration, within physiological limits for 3–5 days. No tolerance was induced with by administration of BLR in normal rabbits, even after 11 iv injections, implying no depletion of bone marrow cells. In contrast, repeated endotoxin injections led to febrile and leukocytic tolerance. In addition, BLR induced normal leukocytosis and a biphasic fever response in endotoxin-tolerant animals. When BLR and endotoxin were mixed and administered every day to rabbits, the animals became tolerant to endotoxin but gave a normal fever and leukocyte response to BLR, even after the 14th injection. The imbalance induced by CP administration in the granulocyte/lymphocyte ratio may be corrected following an injection of BLR. These data showed that the physiological activity of BLR in leukopoiesis was clearly distinguishable from that manifested by E. coli endotoxin and in the second instance by hydrocortisone.