Steroid modulation of naturally occurring diurnal variation in circulating pluripotential haematopoietic cells (CFU‐GEMM)

Abstract

The number of committed granulocyte-monocyte precursors (CFU-GM) in circulation was shown to increase following steroid administration in humans. To see if steroids could be used to improve the collection of peripheral blood stem cells for hematopoietic reconstitution, their effect on circulating CFU-GEMM [granulocytic, erythrocytic, monocytic and megakaryocytic colony forming unit] was investigated. Six healthy young adults, 3 men and 3 women, were given 60 mg of prednisone orally at 0800 h on day 1. Blood CFU-GEMM and committed precursors (CFU-GM and BFU-E) were cultured in methylcellulose. Samples were taken at 1600 h the day before and at 0800 h on the day of steroid administration, and at 4, 8, 24 and, in a few cases, 48 h after steroid. Pre-treatment CFU-GEMM levels (per unit volume of blood) at 1600 h was 180 .+-. 23% (mean .+-. SEM) [standard error of the mean] of that at 0800 h, showing a significant (P < 0.025) diurnal variation. Eight hours after steroids there was a fall in CFU-GEMM to 28 .+-. 4.5% of the 0800 h presteroid level. Twenty-four hours following steroid administration, CFU-GEMM rose significantly (P < 0.05) to 188 .+-. 33% of 0800 h baseline values: CFU-GM and BFU-E [erythrocytic burst-forming cell] changes generally paralleled those noted for CFU-GEMM. Blood levels of CFU-GEMM exhibit a significant diurnal variation. Oral prednisone given 24 h in advance of collection increases the 0800 h value to that found at 1600 h. The steroid effect may be due to a resetting of the diurnal control mechanism. Use of this information may be important in collection of circulating hematopoietic stem cells for use in bone marrow reconstitution in man.