J. K. Millar1, K. B. Kannan2, T. J. Loftus2, I. G. Alamo2, J. Plazas3, P. A. Efron2, A. M. Mohr2 1University Of Florida,College Of Medicine,Gainesville, FL, USA 2University Of Florida,Department Of Surgery And Center For Sepsis And Critical Illness Research,Gainesville, FL, USA 3University Of Florida,Gainesville, FL, USA
Introduction: Following severe injury, a hypercatecholamine state develops that is associated with bone marrow dysfunction characterized by increased mobilization of hematopoietic progenitor cells to the peripheral blood and decreased growth of bone marrow progenitor cells. Bone marrow dysfunction clinically manifests as a persistent injury-associated anemia. Since conditions within the bone marrow microenvironment define the development of erythroid progenitor cells, we sought to determine the influence of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS) on the hematopoietic cytokine response.
Methods: Bone marrow was obtained from male Sprague-Dawley rats (n=6/group) sacrificed seven days after lung contusion and hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1β (IL-1β), interleukin-10 (IL-10), stem cell factor (SCF), transforming growth factor-β (TGF-β), High Mobility Group Box-1 (HMGB-1), and B-cell lymphoma-extra large (Bcl-xL). Data were presented as mean ±standard deviation; *p<0.05 vs. naïve by t-test.
Results: Seven days following LCHS and LCHS/CS, expression of hematopoietic cytokines (IL-1β, IL-10, SCF, and TGF-β) was decreased (Table). Seven days following LCHS and LCHS/CS, expression of HMGB-1, a mediator of granulocyte colony stimulating factor release, was significantly increased (Table). There were no statistically significant differences in cytokine expression between LCHS and LCHS/CS models. Bcl-xL was not affected by LCHS or LCHS/CS (naïve: 44 ±12, LCHS: 44 ±12, LCHS/CS: 37 ±1).
Conclusions: The bone marrow microenvironment was significantly altered following severe trauma. Hematopoietic cytokines were downregulated and the pro-inflammatory cytokine, HMGB-1, was upregulated. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia.
