ghrelin , a 28-amino - acide peptide , is   a potent stimulator of growth hormone release that 
 has been implicated in the control of food intake and energy homeostasis in 
 human begins and rodents 
 [ 15 ] .
ghrelin is not secreted into the gastrointestinal tract like digestive enzymes but into blood vessels to circulate throughout the body .
ghrelin causes weight gain by increasing food intake and reducing fat use [ 7 , 8 ] .
ghrelin has effects on nutrient intake and growth hormone ( gh ) release , subsequently on physical development and growth .
tumor necrosis factor  ( tnf- ) and interleukin-6 ( il-6 ) are pleiotropic cytokines with numerous immunologic and metabolic actions [ 10 , 11 ] .
il-6 is generally considered to be an important cytokine in the network of cytokines that regulate immune reactions and acute phase responses .
the relationship between congenital heart disease ( chd ) , malnutrition , and growth 
 retardation is well documented .
infants with congenital heart disease are prone to malnutrition for several reasons including decreased energy intake , 
 increased energy requirements , or both . different types of cardiac malformations can affect nutrition and growth to varying degrees .
although 
 nutritional and growth status were investigated in children with cyanotic and acyanotic heart disease , serum ghrelin levels have not been established .
the objective of this study is to investigate and compare the functional role of ghrelin on the regulation of energy balance in children with cyanotic and acyanotic congenital heart disease and the association of ghrelin with tnf- , il-6 , that were not entirely confirmed in literature by now .
the study was conducted on 47 children with acyanotic chd , 21 children 
 with cyanotic chd , and 25 healthy children .
all patients ' cardiac diagnoses were 
 made on the basis of clinical and laboratory examinations .
body mass index ( bmi ) 
 was calculated as the ratio of body weight ( kg ) and squared height ( m ) .
all blood samples were drawn at 08 - 09 am and stored 20c 
 until the procedure .
serum ghrelin , tnf- , and il-6 levels were analyzed with 
 elisa kits ( tnf- , il-6 kit was purchased from bio - source   international inc .
( camarillo , calif , usa ) ; ghrelin kit from phoenix international , inc , usa ) .
the given data were compared between groups using one - way anova , followed by post - hoc ; bonferroni test .
in 47 acyanotic patients , mean age was 30.518.4 months , in 21 cyanotic patients was 28.415.6 months and in 25 control subjects was 31.115.1 months .
age and anthropometric data of the patients and the control subjects are shown in table 1 .
there was no significant difference between groups ( the acyanotic patients , the cyanotic patients ) in terms of mean age , weight , height , bmi .
serum ghrelin levels were significantly higher than in acyanotic and cyanotic groups compared to in the control group   ( p<.0001 ) ( table 3 ) . 

serum ghrelin levels in the acyanotic patients were significantly higher than in the cyanotic patients 
 ( p<.0001 ) . 

tnf- 
 levels were significantly higher 
 than in cyanotic and acyanotic patients with chd compared to in the control groups   ( p<.001 , p<.0001 , resp . ) .
serum tnf- values were higher in the acyanotic patients compared to the cyanotic patients with chd ( p<.001 ) .
serum il-6 levels were higher than in cyanotic and acyanotic patients with chd compared to in the control groups   ( p<.0001 , p<.001 , resp . ) . in both acyanotic and cyanotic groups ,
serum ghrelin levels were negatively 
 correlated with bmi ( r=.549 , p<.05 and r=.688 , p<.01 , resp . ) 
				
tnf- levels were not related 
 to bmi in the acyanotic and cyanotic patients with chd .
ghrelin levels were also correlated with tnf- in the acyanotic and cyanotic groups ( r=.485 , p<.05 and r=.573 , p<.01 , resp . )
ghrelin levels were not related to il-6 in the acyanotic and cyanotic patients with chd ( r=.263 , p>.05 and r=.398 , p>.05 , resp . ) .
inadequate caloric intake , 
 malabsorption , and increased energy requirements caused by increased metabolism 
 may all contribute .
however , inadequate caloric intake appears to be the most 
 important cause of growth failure in chd [ 13 , 15 , 16 ] .
patients with acyanotic 
 heart disease had a greater growth deficit in weight , and those with cyanotic 
 heart disease had a greater growth deficit in stature as demonstrated by both 
 decreased height and weight .
although growth impairment is most pronounced in 
 infants with cyanotic chd , growth failure does not correlate well with the 
 degree of hypoxia . in this study ,
the cyanotic patients had a more pronounced 
 retardation in both height and weight than in the acyanotic patients [ 13 , 17 ] .
ghrelin is   accepted as a good marker of the nutritional state , mainly in situations of 
 malnutrition , like anorexia nervosa , owing its fast recovery after weight gain . the inverse correlation between ghrelin levels and bmi
we observed the mentioned correlation , both in children with cyanotic heart disease and in children with acyanotic heart disease .
although the cyanotic patients had a more pronounced retardation in both height and 
 weight than in the acyanotic patients , we found that serum ghrelin levels 
 significantly elevated in the acyanotic patients than in the cyanotic patients 
 ( p<.0001 ) .
growth failure in cyanotic children has not been shown 
 to be proportional to the severity of cyanosis , suggesting that multiple 
 factors are involved in the pathogenesis of their growth disturbance .
alteration of endocrine mediators of growth has been implicated as a possible 
 mechanism of growth failure in cyanotic patients .
cyanotic newborn lambs have 
 decreased levels of serum insulin - like growth factor i without a corresponding 
 decrease in growth hormone or hepatic growth factor receptors .
weintraub et al .   reported that while insulin - like growth factor i levels were linearly related to height and weight in patients with cyanotic lesions , no 
 such correlation was found in their cyanotic patients .
these studies suggest 
 that chronic tissue hypoxia may have independent role in growth failure .
we found that serum tnf- significantly increased in the cyanotic patients and in 
 the acyanotic patients .
similarly , serum il-6 was increased in both groups but the change was more distinctive in the cyanotic patients . tnf- and il-6 appear to be important cachectic process mediators , although this association is not completely established [ 23 , 24 ] .
cachexia results in decreased muscle 
 strength and function and compromised immune function [ 25 , 26 ] .
this syndrome is likely to occur in children who have chronic congestive heart failure , chronic shunt hypoxemia .
in addition to inadequate calorie and protein intake , there is evidence that this syndrome may be caused by circulating tumor necrosis factor , which stimulates catabolism . in the present study , ghrelin correlated to positively with tnf- , in acyanotic patients and cyanotic patients with chd .
the relation of ghrelin with tnf- raises the possibility 
 of the direct effect of tnf- upon ghrelin or the impact of heart failure 
 severity upon both ghrelin and tnf-. nagaya et al .  
have shown that plasma ghrelin level is increased in cachectic patients with congestive heart 
 failure as a compensatory mechanism in response to anabolic - catabolic 
 imbalance . in conclusion ,
serum ghrelin level is elevated in cyanotic and acyanotic patients 
 with chd . increased ghrelin levels
additionally , the relation of ghrelin with cytokines 
 may be explained by the possible effect of chronic congestive heart failure and chronic shunt 
 hypoxemia .
 background / aim . 
 ghrelin has effects on nutrient intake and growth . 
 the cause of growth retardation in congenital heart disease is multifactorial . 
 the aim of the present study is to investigate the ghrelin in congenital heart disease and the association of ghrelin with tnf- and il-6 . 
 
 materials and methods . 
 we measured serum ghrelin , tnf- , and il-6 levels using spesific immunoassay in 68 patients ( 47 acyanotic , 21 cyanotic with congenital heart disease ) and in 25 control subjects . 
 results . in comparison to controls , serum ghrelin , 
 tnf- levels were significantly higher in acyanotic patients and cyanotic patients with congenital heart disease ( p<.0001 ) . 
 in acyanotic and cyanotic patients with congenital heart disease , there was a positive correlation between ghrelin and tnf- ( r=.485 , p<.05 and r=.573 , p<.01 , resp . ) . 
 conclusion . 
 serum ghrelin levels is elevated in acyanotic and cyanotic patients with congenital heart disease . increased ghrelin levels 
 represents malnutrition and growth retardation in these patients . 
 the relation of ghrelin with cytokines may be explained by the possible effect of chronic congestive heart failure and chronic shunt hypoxemia . 
1. INTRODUCTION
2. MATERIAL AND METHODS
3. RESULTS
4. DISCUSSION