pleura is divided into a parietal layer 
 which lines the inner aspect of the chest wall and a visceral 
 layer which covers the interlobar fissures .
fluid 
 collection within the pleural cavity can be assessed with 
 clinical and radiological means .
when pleural effusion is 
 detected , the characteristics of the fluid ( exudate or 
 transudate ) must be revealed using thoracocentesis .
pneumonias 
 and congestive heart failure are the most frequently encountered 
 causes of transudative and exudative effusions , respectively 
 .
accumulating knowledge about cytokines 
 demonstrated their important roles in the pathogenesis of most of 
 the infectious diseases .
interleukins ( ils ) mediate the 
 reactions of the our organism against foreign antigens and harmful 
 agents . the ils act through autocrine or paracrine rather than 
 endocrine pathways . in various infectious diseases significant 
 alterations in il concentrations of blood , as well as of body 
 fluids , occur .
although il levels in serum and various body fluids 
 have been studied in various diseases , very few researches 
 involving il levels in pleural effusions of children have been 
 conducted [ 3 , 4 ] .
it is already acknowledged that 
 established criteria used for the differentiation between 
 exudative and transudative pleural effusions in adults are not 
 valid for children and further studies are required to determine 
 diagnostic criteria for children .
the aim of this study 
 is to compare il levels in exudative and transudative pleural 
 fluids by measuring il levels in pleural effusions developed 
 owing to various etiological factors in childhood .
we aimed to 
 examine whether the changes in pleural fluid protein , glucose , 
 and lactate dehydrogenase ( ldh ) parameters , as well as in 
 il-1 , il-2 , il-6 , and il-8 levels , were significant in 
 differential diagnosis of childhood pleural effusions .
the study group consisted of 26 patients admitted in the 
 department of pediatrics , medical faculty , firat university with a 
 diagnosis of pleural effusions .
thoracal ultrasonograms were 
 obtained from patients thought to have pleural effusions in 
 consideration of medical history , physical examination , and chest 
 x - rays . the presence and the amount of pleural fluids were 
 determined and then thoracocentesis was performed .
all samples 
 were obtained by thoracentesis at the   diagnosis time 
 ( table 1 , figure 1 ) .
the first 
 samples were centrifuged immediately for the measurement of il 
 concentration and the supernatant layers were stored at 
 70c until testing for cytokines .
the second samples 
 were inoculated in aerobic , anaerobic , and lwenstein - jensen 
 media and stained with gram , giemsa , and ziehl - nielsen 
 dyes .
the third samples were analysed for protein , glucose , and 
 ldh . as indicators of infection ,
peripheral leukocyte counts 
 ( wbc ) , erythrocyte sedimentation rate ( esr ) , c - reactive protein 
 ( crp ) measurements , blood culture , and purified protein derivate 
 ( ppd ) tests were performed .
pleural effusions were categorized as exudates and transudates 
 according to the clinical and laboratory findings .
the cutoff values for the differentiation 
 between the pleural transudates and exudates were determined as 
 follows : protein , 3  g / dl ; ldh , 200  iu / l ; pleural 
 fluid / serum protein ratio , 0.5 ; and pleural fluid / serum ldh 
 ratio , 0.6 .
pleural effusions with values above these cutoffs 
 were classified as exudates and those below as transudates . 

empyematous effusions were characterised by 
 the presence of gram - positive bacteria in pleural fluid smears , 
 attendant pneumonia with or without bacterial growth in the 
 cultures of pleural fluid samples , and typical glucose 
 ( < 40 mg / dl ) and/or protein ( > 5  g / dl ) and/or ldh 
 ( > 1000 
the samples of pleural 
 fluids with higher glucose concentrations ( > 40  mg / dl ) whose 
 gram - stained smears did not reveal any specific characteristics 
 or bacterial growth were considered as parapneumonic effusions . 

the patients whose pleural fluid smears revealed afb 
 which could be cultured in lwenstein - jensen media and also 
 responded favorably to the antituberculostatic treatment were 
 acknowledged as cases with tuberculous pleurisy [ 5 , 
 6 , 7 ] .
pleural fluids preserved at 70c were thawed and 
 il-1 , il-2 , il-6 , and il-8 levels in the samples were 
 measured using enzyme - linked immunosorbent assay ( elisa ) and 
 il-1 , il-2 , il-6 , and il-8 bender medsystems commercial kits .
the clinical and laboratory characteristics of the patients were 
 given as means (  standard deviation ( sd ) ) .
statistical 
 evaluations between different groups were done with kruskal - wallis 
 variance analysis and post - hoc tukey - scheffe tests using spss 
 10.0 software programs .
in our study group pleural effusions were of exudative ( n = 27 , 
 75% ) and transudative ( n = 9 , 25% ) type . the ages of the study 
 subjects ranged between 9 months and 14 years .
twelve 
 parapneumonic ( 44% ) , 12 empyematous ( 44% ) , and 3 ( 12% ) 
 tuberculous pleural effusions were detected in the exudate group ( table 1 ) .
a statistically significant difference was found between crp 
 values   of the exudate ( 140.2  92.4  mg / dl ) and the 
 transudate ( 9.6  3.2  mg / dl ) groups ( p < .001 ) 
 ( figure 2 ) .
protein levels 
 in pleural fluids were measured as 5.1  1.2  g / dl and 
 1.6  0.5  g / dl in the exudate and the transudate groups , 
 respectively ( p < .001 ) . glucose levels in pleural fluids were 
 measured as 53.3  36.6  mg / dl in the exudate group and 
 83.8  14.7  mg / dl in the transudate group ( p < .001 ) 
 ( figure 3 ) .
il-1 levels of pleural fluids in the exudate and the 
 transudate groups were detected as 304.1  127.7  pg / ml and 
 70.1  23.4 pg / ml , respectively ( p < .001 ) . 

il-1 levels 
 were demonstrated as 210  43.5  pg / ml in the parapneumonic 
 effusion group , 430.3  69.9 
pg / ml in the empyematous 
 effusion group , and 175.3  36.3  pg / ml in the tuberculous 
 effusion groups .
statistically significantly higher values were 
 found in the empyematous group when compared with the 
 parapneumonic and tuberculous pleural effusion groups ( p < .001 ) .
il-2 concentrations of pleural fluids were ascertained to be at 
 undetectable levels in 12 ( 44.4% ) and 176.6  173.6  pg / ml in 15 ( 55.6% ) patients in the exudate group . 

statistically significant difference was 
 uncovered between the exudate and the transudate groups ( p < .001 ) .
statistically significant differences were not revealed 
 between the empyematous group and the other two groups ( p > .05 ) . 
 statistically significantly higher values were recognized in the 
 tuberculous pleural effusion group rather than the parapneumonic 
 effusion group ( p < .01 ) .
il-6 levels were detected to be 18589.5  3631.8  pg / ml in 
 the exudate group and 65.6  16.0  pg / ml in the transudate 
 group ( p < .001 ) .
the corresponding values were 15295.0  22678.1  pg / ml in the parapneumonic effusion group , 
 20518.0  1410.9 
pg / ml in the tuberculous pleural 
 effusion group . in the empyematous group ,
statistically 
 significantly higher values were obtained when compared with 
 those of the parapneumonic effusion 
 group , while the corresponding values detected in the tuberculous 
 pleural effusion group were also significantly higher than those 
 found in the parapneumonic effusion group ( p < .001 ) .
pg / ml in the exudate group and 108.8  92.0  pg / ml in the transudate group ( p < .001 ) .
the 
 concentrations of il-8 were 1884.5  366.7 in the 
 parapneumonic effusion group , 4789.8  1013.2 
pg / ml in the 
 empyematous effusion group and 919.0  9454.5  pg / ml in the 
 tuberculous pleural effusion group .
the values were statistically 
 significantly higher in the empyematous group when compared with 
 the other two groups ( p < .001 ) ( figure 4 ) .
pleural effusion can be seen due to the intrusion of 
 an infectious agent or an irritating foreign substance inside the 
 pleural cavity or due a direct access of harmful materials or 
 neoplastic cells into the pleural cavity via hematogenous route 
 .
it can be observed following pleural trauma or in 
 association with asbestosis related pleural diseases .
pleural effusions are known to develop 
 secondary to trauma , cardiac , renal , collagenous diseases and 
 malignancies besides pneumonia [ 9 , 
 10 , 
 11 ] . from 
 61% to 80% of the cases with pleural effusions
empyema is also an important cause of 
 mortality in the developing countries . in the remaining 
 20%39% of the cases ,
empyema develops secondary to 
 trauma , malignancies , and renal diseases [ 5 , 
 12 , 13 , 
 14 , 15 ] . 
 in our study group
many studies have been conducted concerning 
 the levels of il-1 , il-2 , il-6 , and il-8 in body fluids in 
 various infections .
although many studies investigating the 
 alterations in levels of il according to the exudative or 
 transudative nature of pleural effusions in adults have been 
 performed , similar studies pertaining to children are relatively 
 few [ 16 , 17 , 
 18 ] .
for that reason many studies have analysed 
 il-1 levels in patients with meningitis , sepsis , urinary 
 tract infections , and empyema .
variable results have been obtained 
 dependent on the presence of different etiological agents 
 [ 17 , 18 ] . in patients with bacterial and tuberculous 
 meningitis ,
il-1 levels of cerebrospinal fluids were found 
 to be significantly higher than those with aseptic meningitis and 
 in the control group .
umblical plasma levels of il-1 of 
 infected newborns with early - onset sepsis were found to be higher 
 than those of the control group .
il-1 levels in synovial 
 fluids were detected to be higher than those in the pediatric 
 cases with   suppurative arthritis due to other causes . 

silva - mejias et al   have found comparatively higher 
 il-1 levels in the empyema group .
similar to our findings , 
 alexandrakis et al   revealed that il-1 levels in 
 pleural effusions were higher in the exudate group compared with 
 those of the transudate group .
naito et al   ascertained 
 that il-1 levels in pleural effusions were higher than 
 those found in bacterial infections due to other causes .
in 
 accordance with the literature in our study , il-1 levels 
 were nearly 4.5 times higher in the exudate group .
il-2 levels in pleural effusions due to malignancies were reported 
 to be lower than those with tuberculous pleural effusions 
 .
shimokata et al 
  stated that il-2 levels were 
 at undetectable levels in 25% of tuberculous pleural effusions 
 and 75% of cancerous pleural effusions . in our study
il-2 levels 
 in pleural fluids were at undetectably lower levels in 44% of 
 the patients in the exudate group while the il-2 levels of the 
 remaining 56% were assessed as 176.6  33.4  pg / ml . 

however all the patients in the transudate group demonstrated 
 undetectable il-2 levels . in our study
a statistically 
 significant difference was not present between the empyema group 
 and the other two groups .
however a statistically significant 
 difference was detected between the parapneumonic and the 
 parapneumonic pleural effusion groups .
various studies have been performed concerning the 
 levels of il-6 which is the mediator and the regulator of 
 inflammatory responses in miscellaneous inflammatory 
 processes .
blood il-6 levels were found to be higher in children 
 with mycoplasma pneumoniae infections who stayed febrile 
 for more than 3 days compared with those having shorter febrile 
 episodes .
they were also 
  statistically significantly higher in pediatric cases 
 with urinary tract infections when compared with the control 
 groups .
il-6 levels of cerebrospinal fluid in the patients with 
 bacterial meningitis were reported to be significantly higher 
 than the aseptic meningitis and in the control groups .
levels above 100  pg / ml were measured in pediatric cases with 
 viral ( 14% ) but especially with bacterial meningitis ( 53% ) . 

xirouchaki et al 
 and yokoyama et al   reported 
 the levels of il-6 in pleural fluids to be significantly higher 
 in the exudate group rather than the transudate group .
they also 
 found il-6 concentrations significantly higher in the tuberculous 
 group rather than the parapneumonic effusion group . in our study 
 not
only the levels of il-6 were different between the groups 
 with parapneumonic and empyematous effusions , but at the same 
 time statistically significant differences were found between the 
 empyematous and the parapneumonic or tuberculous pleural effusion 
 groups .
alexandrakis et al   measured il-6 levels in 
 serum and pleural fluids and ascertained that serum il-6 levels 
 did not differ significantly between the exudate and the 
 transudate groups .
however pleural fluid il-6 levels were 
 detected to be meaningfully higher in the exudate rather than the 
 transudate group . a definite proportion between the serum and 
 pleural fluid il-6 concentrations could not be assessed .
however 
 we found il-6 levels in the pleural fluid to be 285 times higher 
 than those detected in the exudate group .
il-8 is the mediator and the regulator of chemotaxis of 
 leukocytes in inflammatory processes . in adults
il-8 levels 
 were found to be higher in cases with infectious pleural 
 effusions compared with the patients with noninfectious 
  effusions   [ 3 , 26 , 
  27 , 28 , 
  29 , 30 , 
  31 , 32 ] . 

ceyhan et al   reported higher levels in 
 empyematous / parapneumonic effusion groups rather than the 
 tuberculous group .
however antony et al   detected higher 
 levels in cases with parapneumonic effusions unlike those found 
 in the group with tuberculous effusions .
il-8 concentrations in 
 the empyematous group were reported to be higher than those 
 measured in the parapneumonic group . in accordance with this 
 study , in our study the highest levels of il-8 were detected in 
 the empyematous , parapneumonic , and tuberculous pleural effusions 
 in decreasing order .
dlugovitzky et al   discovered 
 statistically significantly higher il-8 values in the tuberculous 
 pleural effusion group in contrast with   findings in the 
 parapneumonic pleural effusion group .
ashitani et al 
 and broaddus et al   found higher levels in the empyema 
 group compared with the other groups .
miller and idell 
 have detected   significantly higher levels in the exudate group 
 rather than the transudate group . in this study ,
similar to the 
 findings of other   investigations , il-8 levels in the exudate 
 group were reported to be 28 times higher than those found in the 
 transudate group .
this study have shown that for the differentiation between the 
 exudative and transudative pleural effusions , in addition to the 
 parametres such as   protein , glucose and ldh , pleural fluid 
 il-1 , il-2 , il-6 , and il-8 levels could be used . 

etiological factors can be differentiated by determining pleural 
 fluid il levels . taking these levels into consideration
accordingly , a definitive diagnosis , a successful 
 treatment and reduction in mortality can be achieved .
 the aim is to examine whether the changes in pleural fluid 
 interleukin ( il)-1 , il-2 , il-6 , and il-8 levels were 
 significant in differential diagnosis of childhood pleural 
 effusions .   
 il-1 , il-2 , il-6 , and il-8 levels in pleural 
 fluids of all 36 patients were measured . 
 the levels of 
 il-1 , il-2 , il-6 , and il-8 in pleural fluids were 
 statistically significantly higher in the transudate group 
 compared with those of the exudate group . 
 the levels of 
 il-1 , il-6 , and il-8 were also found to be statistically 
 significantly higher in the empyema group compared with both the 
 parapneumonic and the tuberculous pleural effusion groups . 
 the 
 levels of il-2 and il-6 were detected to be statistically 
 significantly higher in the tuberculous pleural effusion group in 
 comparison with those of the parapneumonic effusion group . 
  
 the results showed that pleural fluids 
 il-1 , il-2 , il-6 , and il-8 could be used in pleural fluids 
 exudate and transudate distinction . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION