***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Interleukin-1 receptor antagonist ( IL1ra ) has demonstrated efficacy in a wide range of animal models of neuronal injury . We have previously published a r and omised controlled study of IL1ra in human severe TBI , with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines . In this study , we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain . We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury , particularly in sample s from the first 48 h following injury . The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space . Chemokines related to recruitment of macrophages from the plasma compartment ( MCP-1 ) and biasing towards a M1 microglial phenotype ( GM-CSF , IL1 ) are increased in patient sample s in the rhIL1ra-treated patients . In control patients , cytokines and chemokines biased to a M2 microglia phenotype ( IL4 , IL10 , MDC ) are relatively increased . This pattern of response suggests that a simple classification of IL1ra as an ‘ anti-inflammatory ’ cytokine may not be appropriate and highlights the importance of the microglial response to injury Objective : To examine whether acute inflammation profiles predict posttraumatic depression ( PTD ) risk 6 and 12 months after traumatic brain injury . Setting : University-affiliated level 1 trauma center and community . Participants : Adults with moderate to severe traumatic brain injury ( acute serum levels : n = 50 ; acute cerebrospinal fluid ( CSF ) levels : n = 41 ) . Design : Prospect i ve cohort study . Main Measures : Patient Health Question naire ; inflammatory biomarkers ( interleukin [IL]-1&bgr ; , IL-4 , IL-5 , IL-6 , IL-7 , IL-8 , IL-10 , IL-12 , tumor necrosis factor & agr ; , soluble vascular adhesion molecule [ sVCAM-1 ] , soluble intracellular adhesion molecule [ sICAM-1 ] , soluble Fas [ sFAS ] ) . Results : Higher levels of acute CSF cytokine surface markers ( sVCAM-1 , sICAM-1 , and sFAS ) in an inflammatory biomarker risk ( IBR ) score were associated with a 3.920-fold increase in the odds of developing PTD at 6 months ( 95 % confidence interval : 1.163 - 8.672 ) . Having sICAM-1 , sVCAM-1 , or sFAS above the 75th percentile had a positive predictive value of 85.7 % for PTD risk at 6 months . An IBR score including inflammatory biomarkers IL-7 and IL-8 showed a trending association with 12-month PTD risk ( odds ratio = 3.166 , 95 % confidence interval : 0.936 - 10.708 ) . Conclusion : Acute CSF IBR scores show promise for identifying individuals at risk for PTD . Further research should assess acute CSF inflammatory biomarkers ' relationships to chronic inflammation as a mechanism of PTD and should explore anti-inflammatory treatments for PTD , as well as prevention and screening protocol s , and link inflammatory biomarkers to symptom tracking BACKGROUND Secondary brain damage after traumatic brain injury ( TBI ) involves neuro-inflammatory mechanisms , mainly dependent on the intracerebral production of cytokines . In particular , interleukin 1beta ( IL-1beta ) is associated with neuronal damage , while interleukin 6 ( IL-6 ) exerts a neuroprotective role due to its ability to modulate neurotrophins bio synthesis . However , the relationship between these cytokines and neurotrophins with the severity and outcome of TBI remains still controversial . AIMS To determine whether the concentration of IL-1beta and IL-6 and neurotrophins ( nerve growth factor ( NGF ) , brain-derived neurotrophic factor ( BDNF ) , glial-derived neurotrophic factor ( GDNF ) ) in the cerebrospinal fluid ( CSF ) of children with TBI correlates with the severity of the injury and its neurologic outcome . METHODS Prospect i ve observational clinical study in a university hospital .  CSF sample s were collected from 27 children at 2h ( Time T1 ) and 48 h ( Time T2 ) after severe TBI , and from 21 matched controls . Severity of TBI was evaluated by GCS and neurologic outcome by GOS . CSF concentrations of cytokines and neurotrophins were measured by immunoenzymatic assays . RESULTS Early NGF and IL-1beta concentrations ( T1 ) correlated significantly with the severity of head injury , whereas no correlation was found for IL-6 , BDNF , and GDNF . Furthermore , higher NGF and IL-6 and lower IL-1beta expression at T2 were associated with better neurologic outcomes . No significant association was found between BDNF or GDNF expression and neurologic outcome . CONCLUSIONS NGF concentration in CSF is a useful marker of brain damage following severe TBI and its up-regulation , in the first 48 h after head injury together with lower IL-1beta expression , correlates with a favorable neurologic outcome . Clinical and prognostic information may also be obtained from IL-6 expression Studies have characterized absolute levels of multiple inflammatory markers as significant risk factors for poor outcomes after traumatic brain injury ( TBI ) . However , inflammatory marker concentrations are highly inter-related , and production of one may result in the production or regulation of another . Therefore , a more comprehensive characterization of the inflammatory response post-TBI should consider relative levels of markers in the inflammatory pathway . We used principal component analysis ( PCA ) as a dimension-reduction technique to characterize the sets of markers that contribute independently to variability in cerebrospinal ( CSF ) inflammatory profiles after TBI . Using PCA results , we defined groups ( or clusters ) of individuals ( n=111 ) with similar patterns of acute CSF inflammation that were then evaluated in the context of outcome and other relevant CSF and serum biomarkers collected days 0 - 3 and 4 - 5 post-injury . We identified four significant principal components ( PC1-PC4 ) for CSF inflammation from days 0 - 3 , and PC1 accounted for the greatest ( 31 % ) percentage of variance . PC1 was characterized by relatively higher CSF sICAM-1 , sFAS , IL-10 , IL-6 , sVCAM-1 , IL-5 , and IL-8 levels . Cluster analysis then defined two distinct clusters , such that individuals in cluster 1 had highly positive PC1 scores and relatively higher levels of CSF cortisol , progesterone , estradiol , testosterone , brain derived neurotrophic factor ( BDNF ) , and S100b ; this group also had higher serum cortisol and lower serum BDNF . Multinomial logistic regression analyses showed that individuals in cluster 1 had a 10.9 times increased likelihood of GOS scores of 2/3 vs. 4/5 at 6 months compared to cluster 2 , after controlling for covariates . Cluster group did not discriminate between mortality compared to GOS scores of 4/5 after controlling for age and other covariates . Cluster groupings also did not discriminate mortality or 12 month outcomes in multivariate models . PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0 - 3 post-TBI may distinguish individuals with poor 6-month outcome , and future studies should prospect ively vali date these findings . PCA of inflammatory mediators after TBI could aid in prognostication and in identifying patient subgroups for therapeutic interventions Secondary brain damage after traumatic brain injury ( TBI ) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines . Interleukin-6 ( IL-6 ) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor ( NGF ) bio synthesis . However , the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial . We have conducted a prospect i ve observational clinical study to determine whether the concentration of IL-6 and NGF in the cerebrospinal fluid ( CSF ) of children with TBI correlates with the severity of the injury and neurologic outcome of patients . CSF sample s were collected from 29 children at 2 h ( time T1 ) and 48 h ( time T2 ) after severe TBI , and from 31 matched controls . TBI severity was evaluated by Glasgow Coma Scale ( GCS ) and neurologic outcome by Glasgow Outcome Score ( GOS ) . CSF concentrations of IL-6 and NGF were measured by immunoenzymatic assays . Early NGF concentrations ( T1 ) correlated significantly with head injury severity , whereas no correlation was found between GCS and IL-6 . Furthermore , IL-6 and NGF upregulation after injury was associated with better neurologic outcomes . Based on these findings , we posit that NGF expression is a useful marker of brain damage following severe TBI . Moreover , the early upregulation of both IL-6 and NGF , which correlates with a favorable neurologic outcome , may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult This study performed a comprehensive analysis of cerebrospinal fluid ( CSF ) cytokine levels after severe traumatic brain injury ( TBI ) in children using a multiplex bead array assay and to evaluate the effects of moderate hypothermia on cytokine levels . To this end , sample s were collected during two prospect i ve r and omized controlled trials of therapeutic moderate hypothermia in pediatric TBI . Thirty-six children with severe TBI ( Glasgow Coma Scale [ GCS ] score of < or=8 ) and 10 children with negative diagnostic lumbar punctures . All children with TBI had continuous monitoring of intracranial pressure and CSF drainage via an intraventricular catheter . Moderate hypothermia ( 32 - 33 degrees C ) was maintained for 48 h in 17 patients , and they were slowly re-warmed at 48 - 72 h. A multiplex bead array assay was used to analyze serial CSF sample s ( < 18 h , 24 + /- 6 h , 48 + /- 6 h , and 72 + /- 6 h ) for 21 pro- and anti-inflammatory cytokines and chemokines . Interleukin (IL)-8 and transforming growth factor beta were measured by enzyme-linked immunosorbant assay ( ELISA ) . There was a strong correlation ( Spearman correlation coefficient = 0.92 , p < 0.001 ) between multiplex assay and ELISA for IL-8 . Pro-inflammatory IL-1beta , -6 and -12p70 , anti-inflammatory IL-10 and chemokines IL-8 and MIP-1alpha were increased after TBI compared to controls , p < 0.05 ; however , there was no association between cytokines and age , gender , initial GCS , or outcome . Hypothermia did not attenuate the increases in CSF cytokine levels after TBI versus normothermia . This investigation confirmed that the multiplex bead array assay is a useful method to measure CSF cytokine levels .  Severe TBI in infants and children induces increases in pro- and anti-inflammatory cytokines and chemokines . It is the first clinical report of increased levels of MIP-1alpha after TBI in any patient population and the most comprehensive assessment of cytokines after TBI to date . Moderate therapeutic hypothermia did not attenuate the increase in CSF cytokine levels in children after TBI Traumatic brain injury ( TBI ) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers . Interleukin-6 ( IL-6 ) is a pro-inflammatory cytokine known to be elevated after trauma , and a major contributor to the inflammatory response following TBI . Previous studies have investigated associations between IL-6 and outcome following TBI , but to date , studies have been inconsistent in their conclusions . We hypothesized that cohort heterogeneity , temporal inflammatory profiles , and concurrent inflammatory marker associations are critical to characterize when targeting sub population s for anti-inflammatory therapies . Toward this objective , we used serial cerebrospinal fluid ( CSF ) sample s to generate temporal acute IL-6 trajectory ( TRAJ ) profiles in a prospect i ve cohort of adults with severe TBI ( n=114 ) . We examined the impact of injury type on IL-6 profiles , and how IL-6 profiles impact sub-acute ( 2weeks-3months ) serum inflammatory marker load and long-term global outcome 6 - 12months post-injury . There were two distinct acute CSF IL-6 profiles , a high and low TRAJ group . Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale ( GOS ) scores at 6months ( adjusted OR=3.436 , 95 % CI : 1.259 , 9.380 ) . Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ ( p⩽0.05 ) . The two groups did not differ with respect acute serum profiles ; however , individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1β and IL-6 levels compared with the low TRAJ group ( p⩽0.05 ) . Last 
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limited literature available on CMD cytokine  measurement in sTBI , with some preliminary data supporting feasibility of measurement and associations between cytokines and patient outcome .
2 .
Various CSF measured cytokines may be associated with patient outcome at 6 - 12 months , including interleukin (IL)-1b , IL-1ra , IL-6 , IL-8 , IL-10 , and tumor necrosis factor 3 .
There is little to no literature in support of an association between CSF cytokines and neurophysiologic or tissue outcomes .