Steven J Schwulst1, Diane M Trahanas, Rana Saber, Harris Perlman. 1. From the Divisions of Trauma and Critical Care (S.J.S., D.M.T.), Department of Surgery, and Division of Rheumatology (R.S., H.P.), Department of Medicine, Northwestern University, Evanston, Illinois.
Abstract
BACKGROUND: The complex alterations that occur in peripheral immunity after traumatic brain injury (TBI) have been poorly characterized to date. The purpose of this study was to determine the temporal changes in the peripheral immune response after TBI in a murine model of closed head injury. METHODS: C57Bl/6 mice underwent closed head injury via a weight drop technique (n = 5) versus sham injury (n = 3) per time point. Blood, spleen, and thymus were collected, and immune phenotype, cytokine expression, and antibody production were determined via flow cytometry and multiplex immunoassays at 1, 3, 7, 14, 30, and 60 days after injury. RESULTS: TBI results in acute and chronic changes in both the innate and adaptive immune response. TBI resulted in a striking loss of thymocytes as early as 3 days after injury (2.1 × 10 TBI vs. 5.6 × 10 sham, p = 0.001). Similarly, blood monocyte counts were markedly diminished as early as 24 hours after TBI (372 per deciliter TBI vs. 1359 per deciliter sham, p = 0.002) and remained suppressed throughout the first month after injury. At 60 days after injury, monocytes were polarized toward an anti-inflammatory (M2) phenotype. TBI also resulted in diminished interleukin 12 expression from Day 14 after injury throughout the remainder of the observation period. CONCLUSION: TBI results in temporal changes in both the peripheral and the central immune systems culminating in an overall immune suppressed phenotype and anti-inflammatory milieu.
BACKGROUND: The complex alterations that occur in peripheral immunity after traumatic brain injury (TBI) have been poorly characterized to date. The purpose of this study was to determine the temporal changes in the peripheral immune response after TBI in a murine model of closed head injury. METHODS: C57Bl/6 mice underwent closed head injury via a weight drop technique (n = 5) versus sham injury (n = 3) per time point. Blood, spleen, and thymus were collected, and immune phenotype, cytokine expression, and antibody production were determined via flow cytometry and multiplex immunoassays at 1, 3, 7, 14, 30, and 60 days after injury. RESULTS: TBI results in acute and chronic changes in both the innate and adaptive immune response. TBI resulted in a striking loss of thymocytes as early as 3 days after injury (2.1 × 10 TBI vs. 5.6 × 10 sham, p = 0.001). Similarly, blood monocyte counts were markedly diminished as early as 24 hours after TBI (372 per deciliter TBI vs. 1359 per deciliter sham, p = 0.002) and remained suppressed throughout the first month after injury. At 60 days after injury, monocytes were polarized toward an anti-inflammatory (M2) phenotype. TBI also resulted in diminished interleukin 12 expression from Day 14 after injury throughout the remainder of the observation period. CONCLUSION: TBI results in temporal changes in both the peripheral and the central immune systems culminating in an overall immune suppressed phenotype and anti-inflammatory milieu.
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