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ORIGINAL RESEARCH ARTICLE

Psychogenic Stress Prior to Burn Injury Has Differential Effects on Bone Marrow and Cytokine Responses

Amy L. Dugan^*,,1, Sandy Schwemberger^*, Greg J. Noel^*, George Babcock^*,, Cora K. Ogle^*, and Nelson D. Horseman^*,

^* Department of Research, Shriners Hospitals for Children, Cincinnati, Ohio, 45229; Department of Molecular Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, 45267; and Department of Surgery, University of Cincinnati, Cincinnati, Ohio, 45267

To whom requests for reprints should be addressed at ¹ Research, Shriners Hospitals for Children, 3229 Burnet Avenue, Cincinnati, OH 45229. E-mail: duganal{at}ucmail.uc.edu

It is well known that many burn patients experience psychopathological disorders prior to burn injury. However, it is not known whether individuals that have been exposed to chronic psychological stresses will respond differently than unstressed individuals when challenged by a burn injury. In this study, we assessed whether chronic psychogenic stress prior to burn injury had any significant impact on burn injury-induced alterations in the myeloid compartment in the bone marrow and serum cytokine levels utilizing a well-controlled purely psychogenic stress model (predator exposure). Mice were individually caged and exposed to a Long Evans rat for 1 hr a day on 3 consecutive days prior to a 15% total body surface area flame burn. Four days after burn injury, bone marrow and serum were collected to assess myeloid cells and cytokine levels, respectively. Bone marrow cells were cultured in granulocyte-macrophage colony-stimulating factor (GM-CSF) to assess clonogenic ability. Flow cytometry was also used to characterize the populations of myeloid cells based on Gr-1 and CD11b staining intensity and to determine the expression of the macrophage colony-stimulating factor receptor (M-CSFR). Serum was assayed for IL-6, IL-12p70, MCP-1, and IFN- by multiplexed sandwich enzyme-linked immunoabsorbent assay (ELISA). We found that predator exposure prior to burn injury ablated the burn-induced increase in myeloid colony formation and attenuated the burn-induced increases in immature monocytes and immature neutrophils in the bone marrow, as well as MCP-1 levels in the serum. Conversely, psychogenic stress exaggerated the burn-induced increase in the number of M-CSFR-positive cells. This study is the first to show the effects of a pure psychogenic stressor (predator exposure) on burn-induced alterations of the immune system. The clinical ramifications of our findings remain to be elucidated.

Key Words: chronic psychogenic stress • burn injury • bone marrow • MCP-1