A Mathematical Model of Hematopoiesis during Systemic Infection

Chronic critical illness (CCI) is a disease state in which, following an initial insult, a patient neither recovers nor dies but instead remains in a state of critical illness. CCI is characterized by prolonged organ dysfunction, weight loss, and persistent increased vulnerability to infection. Recent data has shown that patients with CCI generally exhibit persistent immune dysfunction, characterized by prolonged elevation of specific pro-inflammatory cytokines. In this paper, we introduce a host response model that couples hematopoiesis dynamics with immune response to infection. Specifically, we incorporate the reactions between pro-inflammatory and anti-inflammatory signals with specific hematopoietic stem cell compartments with a reduced model of acute inflammation. We found that a maladaptive hematopoietic response to pathogenic insult is able to qualitatively reproduce similar behavior to that seen in CCI patients, namely the presence of a persistent, elevated level of pro-inflammatory cytokines. This suggests that maladaptive hematopoietic responses in vivo may play a role in the development of CCI.