Norepinephrine modulates myelopoiesis after experimental thermal injury with sepsis

Objective To determine whether thermal injury and sepsis cause an increase in bone marrow norepinephrine release and whether such a release influences bone marrow monocytopoiesis. Summary Background Data The authors previously demonstrated enhanced bone m arrow monocytopoiesis after burn with sepsis. They also showed that physiol ogic 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 bon e marrow norepinephrine release on increased monocytopoiesis after burn sep sis. Methods Norepinephrine release from bone marrow was determined by tradition al pulse-chase methods. Tissue and bone marrow norepinephrine content was a blated by chemical sympathectomy with 6-hydroxydopamine treatment. Clonogen ic potential in response to colony-stimulating factors was determined in to tal nucleated bone marrow cells. Dual color flow cytometry was used to docu ment the distribution pattern of monocyte progenitors. Results Burn sepsis induced increased norepinephrine release in bone marrow , spleen, and heart. Colony-forming assays demonstrated an increase in resp onsive colonies, which was significantly attenuated when norepinephrine con tent was reduced in animals before burn sepsis, Flow cytometric analysis of early and late monocyte progenitors showed a significantly altered distrib ution profile of monocyte progenitors in norepinephrine-depleted mice compa red with norepinephrine-intact mice. Abrogation of bone marrow norepinephri ne content resulted in a 62% survival rate in burn septic mice compared wit h no survivors in norepinephrine-intact mice. Conclusions These data suggest that enhanced bone marrow norepinephrine rel ease after burn sepsis may play a role in bone marrow monocytopoiesis, thus contributing to the sustenance of inflammation.