191 Treatment with GM-CSF Reverses TBI-Induced Immune Suppression in a Combined Injury Model. (April 2023)

• Record Type: Journal Article
• Authors: Sribnick, Eric Anthony; Warner, Timothy; Hall, Mark
• Is Part Of: Neurosurgery. Volume 69(2023)Supplement 1
• Page Start: 30
• Page End: 31
• Publication Date: 2023-04
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1227/neu.0000000000002375_191
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract : INTRODUCTION: Traumatic brain injury (TBI) is a potentially devastating injury for which there are no pharmacotherapies. Frequently, TBI is accompanied by injuries outside the CNS, and we have previously shown that TBI with concurrent extra-cranial injury reliably leads to post-injury immunosuppression, which puts patients at risk for infection and ultimately a poor outcome. To reverse post-injury immune suppression, we have proposed the use of the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF). METHODS: To induce post-injury immunosuppression, we used a previously described model. 28 day old rats were injured via controlled cortical impact and then had 25% blood volume removed. Following injury, animals were treated with vehicle, 5 μg/kg, or 50 μg/kg GM-CSF daily for 7 days. Blood was obtained pre-injury, and on 1, 3, and 7 days post-injury. Brain and spleen were harvested at 7 days post-injury. Adaptive and innate immune function (measured by ex vivo cytokine production in response to an immunostimulant) were assessed in blood and spleen. Flow cytometry was performed on blood and spleen samples. Cytokine levels at the lesion and penumbra were measured by ELISA. RESULTS: As shown previously, injury induced reduction of both innate and adaptive immune function (approximately 50% decrease), which was reversed with GM-CSF. Treatment with GM-CSF significantly expanded the percentage of monocytes. In spleen, injury was associated with an increase in percentage of CD4 cells expressing programmed death-1 (PD-1), and this was also reversed with GM-CSF. ELISA for cytokines in brain samples from lesion and penumbra from GM-CSF treated animals were not significantly different from vehicle. CONCLUSIONS: These data add to a body of literature suggesting that severe trauma leads to immune suppression. Our findings suggest that treatment with GM-CSF may normalize post-injury immune response.