CYCLICAL NEUTROPENIA AND THE PERIPHERAL CONTROL OF WHITE BLOOD-CELL PRODUCTION

Cyclical neutropenia (CN) is an interesting dynamic hematological dise ase in which the neutrophils spontaneously oscillate from approximatel y normal levels to near zero with a period between 19 and 21 days. In the only known animal model for this disorder, the grey collie, the di sease's single apparent difference from human CN is the smaller period of 11-15 days. CN can be treated using the cytokine G-CSF which decre ases the period (to about 14 days in humans), increases the mean value , and elevates the amplitude of the oscillations. After reviewing the clinical and laboratory data on this disease, we examine the propositi on that CN is due to a loss of stability in the peripheral negative fe edback control of neutrophil production. This is accomplished by the d evelopment of a physiologically realist mathematical model for the sys tem. We conclude that there is no consistent way in which such a desta bilization can give rise to either the clinical or laboratory characte ristics of CN. Rather it seems more likely that the oscillations of CN are generated within the pluripotential stem cell population. (C) 199 8 Academic Press Limited.