***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: BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events One hundred fifteen college students were exposed to an evaluative speech task twice , separated by 2 weeks . At both sessions , we assessed cardiovascular , endocrine , immune , and psychological response at baseline and during the task . We found stability across sessions for stress-induced increases in anxiety and task engagement , heart rate , blood pressure , norpinephrine ( but not epinephrine ) , cortisol , natural killer cell cytotoxicity , and numbers of circulating CD3 + , CD8 + , and CD56 + ( but not CD4 + or CD19 + ) lymphocytes . The stable cardiovascular , immune , and endocrine reactivities were intercorrelated , providing evidence of a unified physiological stress response across these outcomes . Although stable stress-induced increases in task engagement were associated with the physiological stress responses , stress-induced anxiety was not Acute psychosocial stress stimulates transient increases in circulating pro-inflammatory plasma cytokines , but little is known about stress effects on anti-inflammatory cytokines or underlying mechanisms . We investigated the stress kinetics and interrelations of pro- and anti-inflammatory measures on the transcriptional and protein level . Forty-five healthy men were r and omly assigned to either a stress or control group . While the stress group underwent an acute psychosocial stress task , the second group participated in a non-stress control condition . We repeatedly measured before and up to 120min after stress DNA binding activity of the pro-inflammatory transcription factor NF-κB ( NF-κB-BA ) in peripheral blood mononuclear cells , whole-blood mRNA levels of NF-κB , its inhibitor IκBα , and of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6 , and the anti-inflammatory cytokine IL-10 . We also repeatedly measured plasma levels of IL-1ß , IL-6 , and IL-10 . Compared to non-stress , acute stress induced significant and rapid increases in NF-κB-BA and delayed increases in plasma IL-6 and mRNA of IL-1ß , IL-6 , and IκBα ( p's<.045 ) . In the stress group , significant increases over time were also observed for NF-κB mRNA and plasma IL-1ß and IL-10 ( p's<.055 ) . NF-κB-BA correlated significantly with mRNA of IL-1β ( r=.52 , p=.002 ) , NF-κB ( r=.48 , p=.004 ) , and IκBα ( r=.42 , p=.013 ) , and marginally with IL-6 mRNA ( r=.31 , p=.11 ) . Plasma cytokines did not relate to NF-κB-BA or mRNA levels of the respective cytokines . Our data suggest that stress induces increases in NF-κB-BA that relate to subsequent mRNA expression of pro-inflammatory , but not anti-inflammatory cytokines , and of regulatory-cytoplasmic-proteins . The stress-induced increases in plasma cytokines do not seem to derive from de novo synthesis in circulating blood cells Effects of three experimental manipulations : mental stress , relaxation , and a nociceptive inflammatory stimulus , capsaicin , on levels of interleukin-6 ( IL-6 ) were examined . Fifty subjects were  pre-trained in  relaxation and then  r and omized to a stress ( Stroop test ) , relaxation ( tape ) , or control ( video ) manipulation . Subjects participated in an evening reactivity session including 20 min of stress , relaxation , or control followed by a capsaicin injection in the forearm . Cardiovascular variables and levels of IL-6 were measured before and after the manipulation , and at regular intervals up to 60 min post-capsaicin . Group assignment did not differentially affect change in IL-6 over time , either before or after capsaicin . Small but significant increases in IL-6 were seen at 60 min post-capsaicin . These findings suggest that an acute stress manipulation does not modulate IL-6 within this time frame . Although IL-6 did increase following a neurogenic inflammatory stimulus , it did so subsequent to the maximum flare , suggesting that flare mechanisms are independent of IL-6 The pathophysiological mechanisms underlying the association between psychological stress and cardiovascular disease are unclear . Interleukin-1beta ( IL-1beta ) and interleukin-6 ( IL-6 ) are inflammatory cytokines playing a pivotal role in atherosclerosis . IL-1beta activates IL-6 , and both cytokines are produced by peripheral blood mononuclear cells . One mechanism through which stress could promote atherosclerosis is by regulating mononuclear cell cytokine gene expression . We studied cardiovascular and cytokine responses in 32 healthy men participating in two 5-min mental tasks and in 10 controls .  Blood pressure and heart rate , assessed using a Portapres-2 , increased significantly following tasks in all participants . Plasma IL-6 levels , determined by ELISA , also increased following tasks , with maximum levels detected 2h post-stress . Quantitative RT-PCR analysis showed that mononuclear cell IL-1beta gene expression rose significantly at 30 min post-stress and remained elevated at 75 and 120 min . Increases in IL-1beta gene expression correlated positively with plasma IL-6 responses , cardiovascular responses , subjective stress ratings , and anxiety symptoms . No changes were detected in controls . Stress-induced activation of mononuclear IL-1beta is a novel mechanism potentially linking stress and heart disease . This mechanism could also play a role in other inflammatory diseases exacerbated by stress The mechanisms of stress-related immune alterations have not been fully eluci date d. Cell-mediated immune responses as well as antibody and certain cytokines are reported as being suppressed during times of high stress . However , the role of suppression vs dysregulation has not been established in human stress models . The effect of exam stress on regulatory cytokines in 16 healthy medical students was assessed by measuring type-1 ( IFN-gamma ) and type-2 ( IL-10 ) cytokines from 72-h PHA/PMA-stimulated P BMC 4 weeks before and 48 h after exams . Results demonstrated decreased IFN-gamma accompanied by increased IL-10 during exam stress that result ed in a decreased IFN-gamma : IL-10 ratio . There was a significant correlation between the cytokine response to PHA/PMA and number and subjective adjustment to daily hassles . Additionally , students who reported greater levels of loneliness also reported greater numbers of and poorer subjective adjustment to hassles . The differences were consistent in both males and females but did not correlate with AM cortisol levels . Additionally , when individuals were grouped into high vs low preexam hassle levels , the type-1/type-2 shift in the IFN-gamma : IL-10 ratio occurred in the low hassles group only . These data suggest that psychologically stressful situations shift type-1/type-2 cytokine balance toward type-2 and result in an immune dysregulation rather than overall immunosuppression . This may partially explain the increased incidence of type-2-mediated conditions such as increased viral infections , latent viral expression , allergic/asthmatic reactions , and autoimmunity reported during periods of high stress 
    Output:
    
These results extend findings from a prior meta- analysis ( Steptoe et al. , 2007 ) to show reliable increases in circulating IL-6 , IL-1β , IL-10 and TNF-α and stimulated IL-1β , IL-4 and interferon-γ in response to acute stress .
It is possible that these responses contribute to associations between exposure to life challenges and vulnerability to inflammatory disease