G-CSF Control of Neutrophils Dynamics in the Blood

Abstract

White blood cell neutrophil is a key component in the fast initial immune response against bacterial and fungal infections. Granulocyte colony stimulating factor (G-CSF) which is naturally produced in the body, is known to control the neutrophils production in the bone marrow and the neutrophils delivery into the blood. In oncological practice, G-CSF injections are widely used to treat neutropenia (dangerously low levels of neutrophils in the blood) and to prevent the infectious complications that often follow chemotherapy. However, the accurate dynamics of G-CSF neutrophil interaction has not been fully determined and no general scheme exists for an optimal G-CSF application in neutropenia. Here we develop a two-dimensional ordinary differential equation model for the G-CSF-neutrophil dynamics in the blood. The model is built axiomatically by first formally defining from the biology the expected properties of the model, and then deducing the dynamic behavior of the resulting system. The resulting model is structurally stable, and its dynamical features are independent of the precise form of the various rate functions. Choosing a specific form for these functions, three complementary parameter estimation procedures for one clinical (training) data set are utilized. The fully parameterized model (6 parameters) provides adequate predictions for several additional clinical data sets on time scales of several days. We briefly discuss the utility of this relatively simple and robust model in several clinical conditions.