E. Miller1, T. J. Loftus1, J. Millar1, K. Kannan1, I. Alamo1, J. Plazas1, P. Efron1, A. Mohr1 1University Of Florida,Department Of Surgery,Gainesville, FL, USA
Introduction: Attenuating the neuroendocrine stress response with propranolol and clonidine has demonstrated efficacy in abrogating persistent injury-associated anemia. Several hematopoietic cytokines may contribute to this process. We hypothesized that propranolol and clonidine would decrease bone marrow expression of high mobility group box 1 (HMGB1) and increase bone marrow expression of interleukin 1 (IL-1), interleukin 10 (IL-10), stem cell factor (SCF), and B-cell lymphoma-extra large (Bcl-xL).
Methods: Male Sprague-Dawley rats were allocated to naïve control, lung contusion followed by hemorrhagic shock and daily chronic stress (LCHS/CS), LCHS/CS +propranolol, or LCHS/CS +clonidine (n=6-7/group). Chronic stress was performed by placement in a restraint cylinder for two hours daily until sacrifice and bone marrow collection on day seven. Bone marrow expression of HMGB1, IL-1a, IL-1b, IL-10, SCF, and Bcl-xL was assessed by polymerase chain reaction. Ratios of cDNA/B-actin were reported as mean ±standard deviation, ap<0.05 vs. naïve, bp<0.05 vs. untreated counterpart.
Results: Raw bone marrow cytokine expression values are listed in the table. Bone marrow HMGB1 expression was significantly increased following LCHS/CS compared to naïve animals, and was significantly decreased by propranolol (47% decrease, p=0.040) and clonidine (7% decrease, p=0.037). IL-1a was significantly decreased following LCHS/CS, and was significantly increased by propranolol (2,833% increase, p <0.001) and clonidine (1,842% increase, p<0.001). IL-1b was significantly decreased following LCHS/CS, and was significantly increased by propranolol (18,654% increase, p<0.001), and clonidine (10,073% increase, p<0.001). IL-10 was significantly decreased following LCHS/CS, and was not significantly affected by propranolol or clonidine. SCF was significantly decreased following LCHS/CS, and was significantly increased by propranolol (629% increase, p<0.001) and clonidine (468% increase, p<0.001). Bcl-xL was not significantly affected by LCHS/CS, and was significantly increased by propranolol (59% increase, p=0.006) and clonidine (77% increase, p<0.001).
Conclusion: Attenuating the neuroendocrine stress response with propranolol and clonidine modulates the bone marrow cytokine response to severe trauma and chronic stress, favoring effective erythropoiesis. Future research should assess the therapeutic value of propranolol and clonidine to prevent persistent injury-associated anemia among critically ill trauma patients.
