the knowledge about the role of cytokines in psoriasis has developed in the last several years . initially , only th1 cells and cytokines secreted by these cells , like tnf- , ifn- , and il-2 , have been associated with the development and maintenance of chronic inflammatory diseases , such as psoriasis . th1 cells differentiate from naive cd4 + cells in the presence of il-12 , il-18 , and ifn and . it is well known that th1 cytokines have strong inflammatory effects in activating macrophage , neutrophil , and cd8 + cytotoxic t cells . in the 1990s , th17 cells were described as a new t - cell population that produces il-17 , il-6 , il-21 , il-22 , and tnf . transforming growth factor ( tgf)-1 , il-6 , il-23 , and il-15 stimulated initial th17 differentiation from naive t cells . tgf-1 is secreted by activated t cells and it initiates t cell and fibroblast activation , as well as angiogenesis and neovascularization [ 37 ] . il-6 , secreted by macrophages , endothelial cells , and epithelial cells , is responsible for augmentation of keratinocyte hyperplasia and invasion of macrophages and t cells [ 3 , 8 ] . il-15 , produced by monocytes , macrophages , dcs , and t cells , can appear to induce angiogenesis , immune cell recruitment , and activation of keratinocytes [ 4 , 9 , 10 ] . cytokines produced by th17 cells were found to initiate acanthosis , hyperkeratosis , and parakeratosis . th17 cells demonstrated involvement in neutrophil and monocyte chemotaxis , t - cell migration and activation , and neovascularization . th22 cells have been recently described as inflammatory cd4 + t cells that produce cytokines such as il-22 , il-26 , and il-13 of which il-22 is the most important functional cytokine . recent studies indicate that il-6 and tnf- , along with the help of plasmacytoid dendritic cells , can promote the th22 phenotype [ 14 , 16 ] . the differentiation of main three t cell subsets involved in the pathogenesis of psoriasis , as well as th1 , th17 , and th22 cytokine production are illustrated in figure 1 . the aim of the study was to assess the serum levels of some cytokines involved in the th17 and th22 responses in psoriatic patients . the study comprised 60 psoriatic patients , 50 males ( 83.33% ) and 10 females ( 16.67% ) , as well as 30 healthy controls . the studied patients ' age was between 18 and 69 years , 45.6  13.2 years on average . the history of the disease was from 1 to 45 years , 18.7  11.5 years on average . thirty - four of the studied patients ( 40% ) reported two psoriasis exacerbations a year , whereas 9 persons ( 15% ) observed as many as 4 exacerbations a year . the skin lesions severity was assessed with the use of psoriasis area and severity index ( pasi ) , body surface area ( bsa ) , and physician global assessment ( pga ) scores . the pasi value in the studied group was from 4.8 to 64.2 and 15.7  9.7 on average . the bsa value was in the range of 9.096.9% and 31.4  18.2 on average . the pga score was 3 in 24 individuals ( 40% ) , 4 in another 24 individuals ( 40% ) , and 5 in 12 individuals ( 20% ) . blood samples were collected from psoriatic patients and controls and were centrifuged for 15 minutes at 1000  g . then , serum samples were subdivided into small aliquots to be stored at 80c until tested for cytokine levels . elisa kits were used to determine il-6 , il-12 , il-17 , il-20 , il-22 , and il-23 ( r&d systems , minneapolis , mn , usa ) serum levels , according to the manufacturer 's instructions . continuous variables were presented as mean  standard deviation , while categorical variables were presented as absolute and relative frequencies . mann - whitney 's u test was used to compare continuous data between the studied and control groups . the statistical analyses of the conducted study results revealed significantly higher serum levels of il-6 , il-20 , and il-23 in psoriatic patients comparing to healthy controls ( table 1 and figure 2 ) . significant correlations between il-20 , il-22 , il-17 , and psoriasis severity were observed . no significant correlations were found between the concentrations of the studied cytokines and the sex , age , or psoriasis duration in the studied patients ( p > 0.05 ) . significantly higher il-6 values were found in the psoriatic patients in comparison to the control group ( p < 0.001 ) . il-6 contributes to the th17 cell line 's involvement in numerous processes of inflammation and autoimmunity by preventing the proliferation of t regulatory cells . il-17 can induce fibroblasts to produce il-6 potentially activating a positive feedback loop that strengthens th17 inflammation . analyzed 78 studies comparing the serum inflammatory markers , including il-6 , in psoriasis with healthy controls . the study showed that the standardized mean differences were higher in psoriatic patients compared to healthy controls for il-6 . elevated serum il-6 appears to be associated with greater psoriasis severity [ 18 , 21 , 24 ] . it was shown that il-6 might be the biomarker differentiating psoriasis arthritis from psoriasis without joint involvement [ 19 , 22 ] . significantly higher il-20 values were found in the psoriatic patients in comparison to the control group ( p < 0.001 ) . a significant positive correlation between the il-20 concentrations and psoriasis severity measured by the pasi was detected ( p < 0.001 ; r = 0.698 ) . il-20 is produced by keratinocytes in the presence of il-22 , tnf- , and il-17 but not ifn- or il-20 itself [ 15 , 25 ] . il-20 can play an important role in the later effector phase of psoriasis pathogenesis , in which it inhibits the terminal differentiation , increases antimicrobial competence , and production of chemokines for neutrophils in keratinocytes [ 25 , 29 ] . there are not many studies concerning il-20 serum level , but increased levels of il-20 were noted in lesional skin as well as in the blood in psoriatic patients . as in our study , il-20 serum levels correlated with pasi scores . a significantly higher increase in il-22 was observed in psoriatic patients in comparison with the healthy controls ( p < 0.001 ) . a significant positive correlation was found between the il-22 concentration and psoriasis severity measured by both the pasi and bsa score ; that is , p < 0.001 ; r = 0.557 and p < 0.001 ; r = 0.559 , respectively . il-22 is a member of the il-10 cytokines family and is mainly produced by th17 , th22 , and mucosal nk cells [ 3032 ] . il-22 upregulates keratinocyte proliferation and migration , inhibits keratinocyte differentiation by downregulating a variety of genes as filaggrin and involucrin genes [ 33 , 34 ] , and augments the expression of inflammatory molecules by keratinocytes , which leads to an increase in skin thickness in vitro and in vivo [ 3537 ] . il-22 increased the expression of the hbd-2 and hbd-3 in human keratinocytes and mmp1 and mmp3 in the skin [ 3840 ] .   in psoriasis , il-22 is overexpressed most probably as a result of upregulated il-23 and il-6 levels [ 12 , 41 , 42 ] . the treatment with tnf inhibitor ( etanercept ) reduced serum levels of il-17 and il-22 . no significant differences were found in the il-12 and il-23 concentrations between the psoriatic patients and control group ( p > 0.05 ) .   il-23 together with il-12 belongs to the il-12 family and are both structurally related ; il-12 is formed by the p40 and p35 subunits ; il-23 consists of p40 and p19 subunits [ 44 , 45 ] . although both il-12 and il-23 are present in psoriasis , studies support that il-23 , rather than il-12 , is crucial during the pathogenesis of psoriasis . il-23 is overexpressed in psoriasis lesional skin , as shown for example , by increased p40 and p19 mrna levels but not always p35 [ 4654 ] . il-23 is overproduced by dermal dendritic cells [ 48 , 53 ] and keratinocytes   in lesional psoriatic skin . most recent reports show no increased expression of the il-12 in psoriasis [ 3 , 49 , 52 , 53 ] . statistically significant differences in serum il-12 level have been found in psoriatic patients comparing to healthy controls [ 20 , 56 ] . however , there are no significant studies comparing the serum levels of il-23 in psoriatic patients and controls . no significant differences were found in the serum il-17 concentrations between the psoriatic patients and control group ( p > 0.05 ) . a significant positive correlation between the il-17 concentrations and psoriasis severity measured by the pasi was detected ( p < 0.05 ; r = 0.277 ) . il-17 ( il-17a ) is a member of a newly identified cytokine family comprising il-17a , il-17b , il-17c , il-17d , il-17e ( il-25 ) , and il-17f . il-17 and il-17f have a proinflammatory activity inducing the expression of proinflammatory cytokines , colony - stimulating factors , and chemokines from dendritic cells , neutrophils , t cells , monocyte / macrophages , and epithelial cells [ 11 , 44 ] . il-17a and il-17f can mobilize , recruit , and activate neutrophils [ 44 , 57 ] . il-17 is undetectable in normal skin , and biological therapy that inhibits th17 pathways results in reduced expression of il-17 and il-23 and improved disease outcomes [ 11 , 24 , 39 ] . th17 cells and the cytokines produced by these cells are found in increased levels within skin affected by psoriasis [ 31 , 4749 , 5860 ] . statistically significant differences in serum il-17a level have been found in psoriatic patients comparing to healthy controls . il-17 serum levels correlated with the psoriasis area and severity index ( pasi ) . in addition , an analysis of mutual correlations between the concentrations of selected cytokines in the psoriatic patients was conducted . a significant positive correlation between the il-23 and il-17 values was found ( p < 0.05 ; r = 0.271 ) . an increase in the il-23 concentration was accompanied by an increase in the il-17 concentration . in previous studies , it was found that interaction of il-23 with its receptor on th17 cells stimulates the production of il-17 and other related proinflammatory cytokines activates nk cells and regulates antibody production [ 1 , 3 , 44 ] . we believe that the results of our study confirm involvement of th17 and th22 cytokines in psoriasis pathogenesis . elevated il-22 level without increase of il-17 level may suggest that th22 role is more significant in the inflammatory process of psoriasis . very high concentrations of il-22 in the patients ' serum can be connected with intensive il-6 stimulation . il-22 and il-20 itself induce production of il-20 , which is elevated in our study . it seems that il-6 , which initiates th17 and th22 pathways in psoriasis , may be helpful in the clinical practice as a soluble biomarker of the disease activity and its prognosis . the development of new therapeutical strategies targeting the initial step of cytokine network activation , for example , il-6 , may reduce the next events of inflammatory reactions and prevent the psoriasis exacerbation and systemic complications . furthermore , serum levels of il-20 , il-22 , and il-17 , which correlated with the clinical severity and activity of psoriasis , may be objective parameters of successful treatment and may be used in the followup .
introduction . psoriasis is a t cell - mediated inflammatory disease in which pathogenesis t helper ( th ) lymphocytes ( th1 , th17 , and th22 ) play an important role . 
 the aim of the study was to assess the serum levels of some cytokines involved in the th17 and th22 responses in psoriatic patients . 
 material and methods . 
 the study comprised 60 psoriatic patients and 30 healthy controls . in the serum collected from psoriatic patients and healthy controls , the concentrations of il-6 , il-12 , il-17 , il-20 , il-22 , and 
 il-23 were examined with elisa kits . 
 severity of psoriatic skin lesions was assessed by means of pasi , bsa , and pga scores . 
 results . 
 il-6 , il-20 , and il-22 concentrations were significantly higher in psoriatic patients in comparison with the control group . 
 the positive correlations between the concentrations of il-22 and il-20 and severity of psoriasis assessed with pasi and bsa scores as well as il-17 and pasi score were found . 
 there was also a positive correlation between il-23 and il-17 concentrations 
 . conclusions 
 . results of the conducted studies suggest that th22 response may contribute to the skin and systemic inflammatory disease in psoriasis . 
 it seems that early identification of soluble biomarkers and initiation of well - matched treatment may prevent exacerbation and progression of psoriasis .