Norepinephrine modulates myelopoiesis after experimental thermal injury with sepsis.

Abstract

To determine whether thermal injury and sepsis cause an increase in bone marrow norepinephrine release and whether such a release influences bone marrow monocytopoiesis. The authors previously demonstrated enhanced bone marrow monocytopoiesis after burn with sepsis. They also showed that physiologic stress and bacterial challenge without injury could lead to a dynamic release of norepinephrine from the bone marrow compartment. In this study, they sought to determine the potential cause-and-effect relationship of bone marrow norepinephrine release on increased monocytopoiesis after burn sepsis. Norepinephrine release from bone marrow was determined by traditional pulse-chase methods. Tissue and bone marrow norepinephrine content was ablated by chemical sympathectomy with 6-hydroxydopamine treatment. Clonogenic potential in response to colony-stimulating factors was determined in total nucleated bone marrow cells. Dual color flow cytometry was used to document the distribution pattern of monocyte progenitors. Burn sepsis induced increased norepinephrine release in bone marrow, spleen, and heart. Colony-forming assays demonstrated an increase in responsive colonies, which was significantly attenuated when norepinephrine content was reduced in animals before burn sepsis. Flow cytometric analysis of early and late monocyte progenitors showed a significantly altered distribution profile of monocyte progenitors in norepinephrine-depleted mice compared with norepinephrine-intact mice. Abrogation of bone marrow norepinephrine content resulted in a 62% survival rate in burn septic mice compared with no survivors in norepinephrine-intact mice. These data suggest that enhanced bone marrow norepinephrine release after burn sepsis may play a role in bone marrow monocytopoiesis, thus contributing to the sustenance of inflammation.