The effects of propranolol and clonidine on bone marrow expression of hematopoietic cytokines following trauma and chronic stress

Abstract

Attenuating post-injury neuroendocrine stress abrogates persistent injury-associated anemia. Our objective was to examine the mechanisms by which propranolol and clonidine modulate this process. We hypothesized that propranolol and clonidine would decrease bone marrow expression of high-mobility group box-1 (HMGB1) and increase expression of stem cell factor (SCF) and B-cell lymphoma-extra large (Bcl-xL). Male Sprague-Dawley rats were allocated to naïve control, lung contusion followed by hemorrhagic shock (LCHS), or LCHS plus daily chronic restraint stress (LCHS/CS) ±propranolol, ±clonidine. Day seven bone marrow expression of HMGB1, SCF, and Bcl-xL was assessed by polymerase chain reaction. Following LCHS, HMGB1 was decreased by propranolol (49% decrease, p=0.012) and clonidine (54% decrease, p<0.010). SCF was decreased following LCHS/CS, and was increased by propranolol (629% increase, p<0.001) and clonidine (468% increase, p<0.001). Bcl-xL was decreased following LCHS/CS, and was increased by propranolol (59% increase, p=0.006) and clonidine (77% increase, p<0.001). Following severe trauma, propranolol and clonidine abrogate persistent injury-associated anemia by modulating bone marrow cytokines, favoring effective erythropoiesis. Attenuating the post-injury neuroendocrine stress response with propranolol and clonidine has demonstrated efficacy in abrogating persistent injury-associated anemia. Sprague-Dawley rats were subjected to blunt trauma, hemorrhagic shock, and chronic restraint stress, with and without propranolol and clonidine administration immediately following resuscitation. Attenuating the neuroendocrine stress response with propranolol and clonidine modulated the bone marrow cytokine response to severe trauma and chronic stress, favoring effective erythropoiesis.