Adrenergic modulation of erythropoiesis following severe injury is mediated through bone marrow stroma

BACKGROUND: Severe trauma leads to hematopoietic failure and bone marrow (BM) dysfunction that manifests clinically as a persistent anemia and leukopenia. The impact of severe trauma and its associated hyperadrenergic state on erythropoiesis has not been described. The aim of this study was to demonstrate the effects of adrenergic agonists and antagonists on erythropoiesis, both in normal bone marrow mononuclear cells (BMNC) and stroma-depleted BM. METHODS: Urine epinephrine (EPI) and norepinephrine (NE) excretion from severely injured patients was assessed via enzyme-linked immunoadsorbent assay (ELISA). Erythropoiesis was assessed by the growth of erythroid progenitors-erythroid burst forming units and colony forming units (BFU-E and CFU-E)-in normal human BM in the presence of adrenergic agonists and antagonists at varying concentrations. Parallel cultures, depleted of BM stroma by passage through nylon wool columns, were compared. RESULTS: Urine NE excretion was elevated in all samples from days 1 to 10 following injury (average 139 +/- 59 mcg/day vs. control 35 +/- 9 mcg/day). In vitro doses of NE, EPI, and isoproterenol (ISO) exerted a stimulatory effect on BFU-E colony growth in BMNCs (expressed as percentage of control: 324 +/- 30, 272 +/- 16, 212 +/- 95, vs. 100%), but had no effect on stroma-depleted BM. CONCLUSIONS: There is a substantial and persistent hyperadrenergic state seen after severe injury that may last for up to a week. Adrenergic agonists have a clear stimulatory effect on the growth of primitive erythroid precursors in normal BM. The adrenergic stimulus appears to be mediated via BM stroma.