proinflammatory cytokines ( il-1 , il-6 , and tnf- ) may significantly influence the development of obesity and concomitant disorders such as type 2 diabetes , arterial hypertension and metabolic disorders .
it is suggested , that il-6 may affect the increase of free fatty acids level .
tnf- is secreted mainly by macrophages and lymphocytes in response to cell damage caused by infection or malignant transformation .
however , it can be also secreted by many other type of cells and tissues , e.g. , adipocytes .
tnf- , similarly to il-6 , is a proinflammatory cytokine , characterized by a broad spectrum of functions which also include cytotoxic and cytostatic effects against cancer cells .
it is able to inhibit lipoprotein lipase ( lpl ) at both mrna and protein levels .
it also inhibits the expression of two major adipose tissue differentiation regulators : ccaat transcription factor that increases binding of alpha proteins ( cebp- ) and nuclear receptor ppar-2 . in consequence , changes in the expression of adipose tissue proteins , such as lpl , ap2 , fatty acid synthase , acetyl - coa carboxylase , glycerol 3-phosphate dehydrogenase ( gpdh ) , glucose receptor glut-4 , and others are observed .
the aim of the present study was to assess the relation between il-6 and tnf- levels in serum of obese and normal weight subjects and to relate it to the crp concentration in obese subjects .
the study was performed in accordance with the declaration of helsinki for human research and study protocol was approved by the ethics committee of warsaw medical university in warsaw , poland .
kg / m , including 54 males aged 31 - 77 ( mean 53  1se years ) and 26 females aged 39 - 75 ( mean 61  2 years ) .
a control group included 53 healthy subjects with normal weight , bmi < 25 ; 24 males aged 22 - 72 ( mean 39  2.3 years ) and 29 females aged 23 - 78 ( mean 47  2.4 years ) . in the studied population
the tests were performed in a disease - free period , at least 3 weeks after any last infection , antibiotic treatment , and at least 3 months after any severe disease .
blood samples were collected using edta as anticoagulant . to determine blood plasma concentration of il-6 and tnf , ' quantikine human il-6 ' and ' quantikine human tnf ' ( r&d systems , mn , usa ) elisa assay kits , respectively , were used .
the measurements were taken using a microplate reader stat fax 2100 ( awareness technology , usa ) .
crp plasma concentration was determined with fixed - point immuno - rate method ( ortho - clinical - diagnostics ) .
results were analyzed for the whole population as well as in relation to gender , and compared with the control group .
mean cytokine levels in different groups were compared with the mann - whitney u test .
the mean il-6 level was generally lower in the control group in comparison with the population of patients population . however , a statistically significant difference in il-6 was found only between obese and normal weight women ( p = 0.001 ) , and not in males .
the highest difference was found again with respect to the group of women ( p < 0.001 ) .
in addition , il-6 level was higher in the obese patients with type 2 diabetes in comparison with the non - diabetic obese patients . here again , a statistically significant difference was observed only in the group of women ( p = 0.01 ) .
the obese diabetic patients had a slightly higher tnf concentration than the obese non - diabetic patients ; the highest , albeit insignificant , difference being in the group of obese women .
statistical analysis showed a positive correlation between il-6 and tnf concentrations ; significant values were achieved for the whole groups of overweight and obese patients ( p = 0.005 ) ( figure 1 ) . in whole populations , regardless of gender , a simultaneous elevation of both proinflammatory cytokines was observed .
correlation between serum concentrations of il-6 and tnf ( r = 0.3 ; p = 0.005 ) .
the crp level positively correlated with the il-6 concentration . here , the results for the whole overweight and obese group as well as in the women group were statistically significant .
no statistically significant correlation between tnf and crp concentrations in overweight and obese patients was evident .
correlation between il-6 concentration and crp level in the population of overweight and obese patients ( r = 0.3 ; p = 0.007 ) .
the crp level significantly correlated with the obesity index expressed by bmi ; the correlation was observed in all analyzed subgroups ( figure 3 ) .
correlation between bmi values and crp levels in the population of overweight and obese patients ( r = 0.4 ; p < 0.001 ) .
it is widely suggested that overweight and obese subjects have elevated concentrations of inflammatory cytokines in serum .
a possible mechanism of obesity - induced inflammatory response is based on the development of oxidative stress which , in consequence , leads to the inflammatory response induced by excessive intake of carbohydrates , mainly glucose .
recent studies have shown that up to 30% of il-6 in the blood stream is secreted by adipose tissue , and the cytokine level positively correlates with body mass index ( bmi ) .
intraperitoneal adipose tissue secretes three times more of il-6 than does subcutaneous adipose tissue . in the present study ,
moreover , a difference was observed in the population of obese , diabetic women in comparison with the women with no symptoms of diabetes .
the obtained results suggest that gender is a major factor influencing the regulation of inflammatory factors ; possibly due to a specific hormonal balance or adipose tissue distribution in women .
some authors consider both type 2 diabetes and insulin resistance as symptoms of an inflammatory response in the organism .
the hypothesis can be confirmed by the increase in acute phase proteins , such as crp , amyloid a , alpha-1-acid glycoprotein , sialic acid , and cortisone in diabetic patients .
the increase in il-6 , parallel to the elevated glucose and insulin concentrations , suggest a possible involvement of the cytokine in glucose metabolism , especially in adipocytes . likewise , in the present study we observed that cytokines positively correlated with the crp level , while crp , in turn , positively correlated with bmi in all analyzed subpopulations of obese patients .
the increase in tnf expression in muscles and adipose tissue , through the tnf ability to phosphorylate serine residues in irs - i ( insulin receptor substrate 1 ) and a consequent decrease of insulin receptor tyrosine kinase activity , can lead to insulin resistance .
the increase of tnf expression in the obese patients definitely demonstrated in the present study , can be a limiting factor for further enlargement of adipose tissue through the induction of insulin resistance of adipocytes .
insulin resistance can influence lipoprotein lipase ( lpl ) activity and hence prevent excessive growth of adipose tissue .
a high adipose tissue lpl to muscle lpl ratio observed in hyperinsulinemia leads to increased transport of lipids to the adipose tissue .
so , rising insulin resistance will cause the reversal of the adipose tissue lpl to muscle lpl ratio , and in that way prevent further growth of adipose tissue .
we suppose that tnf - induced insulin resistance , hyperinsulinemia , and higher lpl activity in adipocytes can cause body fat accumulation . on the other hand ,
the increase in body fat may lead to increased secretion of tnf that , in consequence , can cause insulin resistance .
it is hard to state unambiguously whether the body fat content is a cause or a consequence of the observed differences in tnf concentration .
however , it seems that the development type 2 diabetes depends on a number of other factors being more potent that tnf , as we did not find any differences in the tnf levels between the obese diabetics and non - obese patients with no diabetes .
 backgroundthe development of obesity and related disorders , e.g. , type ii diabetes ( t2d ) , hypertension , and metabolic disturbances is strongly related to increased levels in proinflammatory cytokines ( il-1 , il-6 , and tnf- ) . both il-6 and tnf- 
 are secreted by adipocytes and their concentration correlates with the percentage and distribution of fat tissue in the body . 
 both cytokines are the main factors responsible for the induction of acute phase proteins production ( e.g. , crp ) and to inflammatory state.objectiveto compare of tnf- and il-6 concentrations in serum from obese subjects with those in subjects with normal bmi and to analyze the relation between tnf- , il-6 , bmi and the inflammatory state as measured by the level of crp.material and methodsthe study included 80 obese subject ( 54 males and 26 females ) bmi > 25 kg / m2 . a control group consisted of 53 healthy subjects ( 24 males and 29 females ) with bmi < 25 kg / m2 . to determine the blood plasma concentration of il-6 and tnf , commercial elisa assay kits were used.resultsthe concentration of il-6 was lower in the control compared with the obese patients , but a significance difference concerned only female subjects ( p = 0.001 ) . 
 tnf- concentration was significantly higher in all obese subjects ( p < 0.001 ) . a higher level of this cytokine was also found in patients with obesity suffering from t2 dm . 
 a positive correlation was present between il-6 and tnf- concentrations . 
 only did the il-6 level correlate with the concentration of crp in serum.conclusionsthe study confirmed that increased inflammatory cytokines lead to the persistence of inflammation in obese subjects . 
 however , some other factors , such as gender , may contribute to the development of obesity - related inflammatory states . 
Introduction
Materials and methods
Results
Discussion
Conflicts of interest