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

Summary. The number of committed granulocyte‐monocyte precursors (CFU‐GM) in circulation has been 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 haematopoietic reconstitution, their effect on circulating CFU‐GEMM was investigated. Six healthy young adults, three men and three women, were given 60 mg of prednisone orally at 8 a.m. on day 1. Blood CFU‐GEMM and committed precursors (CFU‐GM and BFU‐E) were cultured in methylcellulose. Samples were taken at 4 p.m. the day before and at 8 a.m. 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 4 p.m. was 180 ± 23% (mean ± SEM) of that at 8 a.m., showing a significant (P < 0·025) diurnal variation. 8 h after steroids there was a fall in CFU‐GEMM to 28 ± 4·5% of the 8 a.m. presteroid level. 24 h following steroid administration, CFU‐GEMM rose significantly (P < 0·05) to 188 ± 33% of 8 a.m. baseline values; CFU‐GM and BFU‐E changes generally paralleled those noted for CFU‐GEMM. These results suggest that blood levels of CFU‐GEMM exhibit a significant diurnal variation. Oral prednisone given 24 h in advance of collection increases the 8 a.m. value to that found at 4 p.m. 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 haematopoietic stem cells for use in bone marrow reconstitution in man.