Cyclical Neutropenia and the Peripheral Control of White Blood Cell Production

Cyclical neutropenia (CN) is an interesting dynamic hematological disease in which the neutrophils spontaneously oscillate from approximately 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 diseaseʹs single apparent difference from human CN is the smaller period of 11–15 days. CN can be treated using the cytokine G-CSF which decreases 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 proposition that CN is due to a loss of stability in the peripheral negative feedback control of neutrophil production. This is accomplished by the development of a physiologically realist mathematical model for the system. We conclude that there is no consistent way in which such a destabilization can give rise to either the clinical or laboratory characteristics of CN. Rather it seems more likely that the oscillations of CN are generated within the pluripotential stem cell population.