PMID- 29421977
OWN - NLM
STAT- MEDLINE
DCOM- 20191007
LR  - 20191007
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 35
IP  - 13
DP  - 2018 Jul 1
TI  - Chronic Alterations in Systemic Immune Function after Traumatic Brain Injury.
PG  - 1419-1436
LID - 10.1089/neu.2017.5399 [doi]
AB  - There is a compelling link between severe brain trauma and immunosuppression in 
      patients with traumatic brain injury (TBI). Although acute changes in the 
      systemic immune compartment have been linked to outcome severity, the long-term 
      consequences of TBI on systemic immune function are unknown. Here, adult male 
      C57Bl/6 mice underwent moderate-level controlled cortical impact (CCI) or sham 
      surgery, and systemic immune function was evaluated at 1, 3, 7, 14, and 60 days 
      post-injury. Bone marrow, blood, thymus, and spleen were examined by flow 
      cytometry to assess changes in immune composition, reactive oxygen species (ROS) 
      production, phagocytic activity, and cytokine production. Bone marrow derived 
      macrophages (BMDMs) from sham and 60-day CCI mice were cultured for immune 
      challenge studies using lipopolysaccharide (LPS) and interleukin-4 (IL-4) models. 
      Acutely, TBI caused robust bone marrow activation and neutrophilia. Neutrophils 
      and monocytes exhibited impairments in respiratory burst, cytokine production, 
      and phagocytosis; in contrast, ROS levels and pro-inflammatory cytokine 
      production were chronically elevated at 60 days post-injury. Cultures of BMDMs 
      from chronic CCI mice demonstrated defects in LPS- and IL-4-induced polarization 
      when compared with stimulated BMDMs from sham mice. TBI also caused thymic 
      involution, inverted CD4:CD8 ratios, chronic T lymphopenia, greater memory 
      conversion, increased T cell activation, impaired interferon gamma induction, and 
      chronically elevated Th1 cytokine and ROS production. Collectively, our in-depth 
      phenotypic and functional analyses demonstrate that TBI induces widespread 
      suppression of innate and adaptive immune responses after TBI. Moreover, at 
      chronic time points, TBI mice exhibit hallmarks of accelerated immune aging, 
      displaying chronic deficits in systemic immune function.
FAU - Ritzel, Rodney M
AU  - Ritzel RM
AD  - Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
FAU - Doran, Sarah J
AU  - Doran SJ
AD  - Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
FAU - Barrett, James P
AU  - Barrett JP
AD  - Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
FAU - Henry, Rebecca J
AU  - Henry RJ
AD  - Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
FAU - Ma, Elise L
AU  - Ma EL
AD  - Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
FAU - Faden, Alan I
AU  - Faden AI
AD  - Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
FAU - Loane, David J
AU  - Loane DJ
AD  - Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology 
      Research (STAR), University of Maryland School of Medicine , Baltimore, Maryland.
LA  - eng
GR  - P30 AG028747/AG/NIA NIH HHS/United States
GR  - R01 NS037313/NS/NINDS NIH HHS/United States
GR  - T32 AI095190/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180503
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
SB  - IM
MH  - Adaptive Immunity/*immunology
MH  - Animals
MH  - Brain Injuries, Traumatic/*immunology
MH  - Immunity, Innate/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC5998829
OTO - NOTNLM
OT  - chronic inflammation
OT  - immunosuppression
OT  - systemic immunity
OT  - traumatic brain injury
COIS- No competing financial interests exist.
EDAT- 2018/02/10 06:00
MHDA- 2019/10/08 06:00
PMCR- 2019/07/01
CRDT- 2018/02/10 06:00
PHST- 2018/02/10 06:00 [pubmed]
PHST- 2019/10/08 06:00 [medline]
PHST- 2018/02/10 06:00 [entrez]
PHST- 2019/07/01 00:00 [pmc-release]
AID - 10.1089/neu.2017.5399 [pii]
AID - 10.1089/neu.2017.5399 [doi]
PST - ppublish
SO  - J Neurotrauma. 2018 Jul 1;35(13):1419-1436. doi: 10.1089/neu.2017.5399. Epub 2018 
      May 3.