negative emotions are associated with increased production of pro - inflammatory cytokines 
 including tumor necrosis factor - alpha ( tnf- ) and interleukin-6 ( il-6)1 , 2 . 

episodic psychological risk factors such as depression have been associated with poor 
 prognosis in cardiovascular disease ( cvd)3 , 4 .
chronic psychological risk factors may also 
 affect the clinical manifestations of heart disease5 , but individual differences in personality traits have received 
 little attention to date in behavioral immunology research6 , 7 .
type d personality has 
 been associated with increased levels of inflammatory biomarkers8,9,10,11 and unfavorable cytokine 
 profiles11 in cvd .
preliminary findings 
 for a group of 42 male patients with chronic heart failure ( chf ) suggested that type d 
 personality was associated with the activated immune system characteristic of heart failure 
 syndrome9 .
the study revealed that , 
 circulating levels of the pro - inflammatory cytokine tnf- were 
 significantly higher in type d patients than in not - type d patients9 .
type d personality was also independently associated with 
 increased circulating levels of tnf- in a subsequent study of chf 
 patients8 .
we hypothesized that type d 
 personality is independently related to immune activation in patients with chf and severely 
 depressed left ventricular function8 .
few 
 studies have investigated whether type d personality is a physiological factor deciding 
 cytokine concentration increases in cvd .
pro - inflammatory cytokines indicate potential onset 
 of disease in cvd symptom - free people and physical activity or exercise can lower the 
 potential risk levels of cvd12 .
regular aerobic exercise reduces cvd risk factors and levels of oxidative stress , and has a 
 positive influence on lipoprotein metabolism13 .
also it is reported that meditation increases the nitrogen oxide , 
 a strong vasodilator , level in the body and improves cardiovascular functioning and 
 arteriosclerosis14 .
therefore , the aim of this study was to search for an association of type d personality 
 with pro - inflammatory cytokine levels , through comparison of the pro - inflammatory cytokine 
 levels of middle - aged women who performed an exercise intervention .
the characteristics of the 
 participants are shown in table 1table 1.characteristics of the subjectsvariablesgroupsmsage ( years)type dexercise47.831.75no - exercise47.582.50not - type dexercise46.582.43no - exercise46.731.90height ( cm)type dexercise156.554.93no - exercise157.194.74not - type dexercise157.286.16no - exercise157.865.31weight ( kg)type dexercise69.219.99no - exercise66.818.00not - type dexercise66.434.00no - exercise66.893.73 .
the participants were allocated to one of the following four groups : type d 
 personality+exercise ( n=12 ) , type d+no - exercise ( n=12 ) , 
 not - type d+exercise ( n=12 ) , and not - type d+no - exercise 
 ( n=10 ) .
all participants completed the 14-item type d scale ( ds14 ) to 
 assess whether or not they had a type d personality .
the ds14 consists of two subscales , 
 negative affectivity ( na ) and social inhibition ( si ) , both of which comprise 7 items .
a 
 standardized cutoff score  10 on both subscales is used to classify a person as having a 
 type d personality . in this study , a korean version of the ds14 developed by lim et al . was 
 used15 .
cronbach s alpha is 0.82 for 
 the na subscale and 0.80 for the si subscale .
subjects who reported going through menopause , 
 drinking , smoking , and performing regular exercise in the past 6 months were excluded from 
 this study .
the sample size of this study was estimated prior to data collection by using a 
 power analysis method as previously suggested16 . assuming a medium effect size of 0.25 and an alpha level of 0.05 , 

all experiments were 
 reviewed and approved by the committee of the kangwon national university .
they were processed under the same conditions before 
 exercise and 10 months after exercise .
blood glucose was measured by the hexokinase 
 method17 . an enzyme - linked 
 immunosorbent assay ( elisa )
was used to measure circulating plasma levels of 
 tnf- and il-6 ( quantikine hs , r&d systems , minneapolis , usa ) . an 
 aerobic exercise program and meditation were performed by the exercise groups three times a 
 week for 10 months . the aerobic exercise program consisted of three parts : a warm - up , 
 walking and running , and cool - down . before starting walking and running on a treadmill , all 
 the subjects performed stretching for 10  min .
this was followed by walking and running on a 
 treadmill at 60 to 70% of hrmax13 , 18 for 40  min . in order to accurately check 
 whether the exercise was conducted within the set range of exercise intensity , we monitored 
 the heart rated of the subjects with a wearable automatic portable heart rate meter ( polar 
 electro , kempele , finland ) .
the subjects were 
 asked to sit in the pyramid sitting position and to concentrate on breathing only ; 
 therefore , the subjects took only deep breaths using their diaphragm rather than short , 
 shallow breaths from their chest until they felt calm .
the ratio of inspiration to 
 expiration breathing began at 1:1 and the ratio was increased to 1:2 .
two - way repeated measures anova was 
 performed to examine differences between type d personality and not - type d. when a 
 significant interaction effect was found between main effects , the paired t - test was 
 performed to compare the effects between groups by time . for comparison of groups by time
spss for windows version 20.0 was 
 used for the statistical analysis , and values of p<0.05 were considered statistically 
 significant .
the changes in glucose and pro - inflammatory cytokines after 10 months of exercise are shown 
 in table 2table 2.the changes in glucose and pro - inflammatory cytokinesvariablesgroupsbeforeafterdifferencep - valueduncanfasting glucose ( mg / dl)type dexercise103.9211.0689.927.4914.00no - exercise104.0812.54104.0812.620.00group < 0.001c , a < d , bnot - type dexercise95.928.8584.753.5211.17time 0.060no - exercise100.7311.96101.0011.520.27grouptime 0.034tnf- ( pg / ml)type dexercise8.102.126.731.7716.91no - exercise7.971.988.152.272.26group 0.015c < d , a , bnot - type dexercise7.041.705.551.5021.16time 0.092no - exercise7.171.707.181.680.14grouptime 0.276il-6 ( pg / ml)type dexercise8.892.047.171.9119.35***no - exercise8.312.118.302.120.12group 0.014c < d , a , bnot - type dexercise7.401.975.672.0123.38***time 0.044no - exercise7.232.027.232.000.00grouptime 0.253meansd . * * * p<0.001 ; * * p<0.01 ; * p<0.05 ( by paired t - test ) . a , type 
 d+exercise ( n=12 ) ; b , type d+no - exercise ( n=12 ) ; c , not - type d+exercise ( n=12 ) ; d , 
 not - type d+no - exercise ( n=10 ) .
the fasting glucose showed a significant interaction effect among the groups 
 ( p<0.001 ) , and grouptime ( p=0.034 ) , and post hoc test results .
the values of the type d 
 groups were significantly higher than those of the not - type d groups .
the 
 tnf- levels showed significant differences among the groups ( p=0.015 ) , 
 and that of the not - type d+exercise group was lower than those of the other three groups . 

the il-6 levels showed significant differences among the groups ( p=0.014 ) , and times 
 ( p=0.044 ) , and was significantly lower in the exercise groups than in the no - exercise 
 groups .
meansd . * * * p<0.001 ; * * p<0.01 ; * p<0.05 ( by paired t - test ) . a , type 
 d+exercise ( n=12 )
; b , type d+no - exercise ( n=12 ) ; c , not - type d+exercise ( n=12 ) ; d , 
 not - type d+no - exercise ( n=10 )
tnf- and il-6 blood levels of obesity or diabetic patients are 
 significantly higher than those of normal subjects19
. excessive accumulation of body fat due to obesity and overweight 
 increases blood cytokine levels such as those of tnf- and il-6 . 

ultimately , this increase causes insulin degradation of the liver and skeletal muscle , and 
 increases the risk levels of various degenerative disorders including metabolic syndrome and 
 insulin resistance9 , 12 .
tnf- and il-6 have been shown to be implicated 
 in the pathogenesis of cvd20 .
il-6 
 stimulates the production of c - reactive protein and fibrinogen6 , and has been associated with increased mortality in cvd21 .
the most studied inflammatory marker in 
 cvd is tnf-. increased circulating levels of 
 tnf- have been related to recurrent cardiac events following myocardial 
 infarction and increased mortality in cvd21 . in addition , blood levels of tnf- and il-6 are closely related with 
 metabolic diseases including obesity and type 2 diabetes mellitus .
our results are 
 consistent with the results of previous studies22 showing that tnf- and il-6 levels of obese 
 patients are significantly decreased by moderate walking exercise . for example , kondo et 
 al.23 measured the body fat and serum 
 cytokine levels of women who participated in an exercise program for seven months .
the body 
 fat and body mass index ( bmi ) of both the normal group and the obese group significantly 
 improved and the blood levels of tnf- and il-6 were more significantly 
 improved in the obese group than in the normal group .
that the blood level of il-6 was 
 significantly improved by a lifestyle modification program prescribing diet and exercise , 
 and stress coping tips for 12 weeks .
the cytokine levels of type d personality subjects increase by more than those of the 
 not - type d personality subjects when under stress25 and type d subjects precursors of inflammatory response9 , and tnf- levels 
 increase5 . in this respect ,
the results 
 of this study indicate that the reduction of tnf- and il-6 blood levels 
 observed after exercise may be a secondary outcome dependent on the decrease in body fat and 
 waist circumference due to exercise , and we judge that the reduction of insulin resistance 
 cytokine expression improves insulin sensitivity contributing to decrease in cvd risk 
 factors . in summary
, the results of this study not only suggest the potential role of personality , 
 they also indicate that personality may affect the established effect of exercise on 
 cytokine activity .
type d personality was independently associated with significant immune 
 activation , and the increase in tnf- activity observed among the type d 
 participants .
 [ purpose ] the purpose of this study was to investigate the effects of exercise therapy on 
 glucose , tnf- and il-6 blood levels in middle - aged women . 
 [ subjects ] a total of 46 
 participants were assigned to four groups : type d personality+exercise 
 ( n=12 ) , type d+no - exercise ( n=12 ) , not - type d+exercise 
 ( n=12 ) , and not - type d+no - exercise ( n=10 ) . [ methods ] 
 blood glucose was measured by the hexokinase method . 
 an enzyme - linked immunosorbent assay 
 ( elisa ) was used to measure the circulating plasma levels of tnf- and 
 il-6 ( quantikine hs , r&d systems , minneapolis , usa ) . an aerobic exercise program and 
 meditation 
 were conducted in parallel by the exercise groups for 10 months . 
 stretching was 
 performed for 10  min as a warm - up , and then walking and running on a treadmill at 60 to 
 70% of hrmax were performed for 40  min three times a week . 
 blood samples were processed 
 according to standard laboratory procedures . 
 [ results ] fasting glucose showed a 
 significant interaction effect among groups , grouptime , and post - test . 
 
 tnf- showed a significant difference among groups , and was lower in 
 the not - type d personality+exercise group than in the other three groups . 
 il-6 showed a 
 significant difference among the groups . 
 [ conclusion ] in conclusion , personality may 
 affect the established effect of exercise on cytokine activity . 
 type d personality was 
 independently associated with significant immune activation , and increase in 
 tnf- activity was observed among type d participants . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION