alopecia areata ( aa ) is common cause of reversible hair loss afflicting approximately 1 to 2% of the general population .
a wide range of clinical presentations can occur , from a single patch of hair loss to complete loss of hair on the scalp ( alopecia totalis , at ) or over the entire body ( alopecia universalis , au ) .
the cause of aa is unknown , although there is evidence to suggest that the link between lymphocytic infiltration of the follicle and the disruption of the hair follicle cycle in aa may be provided by a combination of factors , including cytokine release , cytotoxic t - cell activity , and apoptosis .
it is also considered that a disequilibrium in the production of cytokines , with a relative excess of proinflammatory and th1 types , vs. anti - inflammatory cytokines may be involved in the persistence of aa lesions , as shown in human scalp biopsies .
tumor necrosis factor - alpha ( tnf- ) is a multifunctional proinflammatory cytokine which has been implicated in the pathogenesis of several chronic inflammatory disorders with an autoimmune component .
this cytokine is synthesized in epidermal keratinocytes along with several other cytokines and is known to be a very potent inhibitor of proliferation .
the changes in serum tnf- levels were found in many diseases , such as psoriasis and systemic lupus erythematosus . in some of these diseases , serum tnf- concentration correlated with activity and intensity of the disease , and
although it is well known that multiple cytokines simultaneously play role in aa , many authors have measured only one particular cytokine . our study has focused only on tnf- because there are only a few studies that have measured the serum levels of this cytokine with controversial results .
therefore , the aim of our study was to evaluate serum levels of tnf- in aa patients and control subjects , and also to assess the difference between the localized and extensive forms of the disease such as at and au .
the study included 60 patients with aa ( 36 females and 24 males ; median age , 35.6 years ) .
forty - six patients had localized aa ( laa ) and 14 patients had at , au , or at / au .
the patients who had received any treatment within previous 3 months were excluded from the study , as well as patients with any diseases based on the immune pathomechanism , which could influence serum concentrations of tnf-. control group consisted of 20 generally healthy subjects ( 11 females and 9 males ; median age , 32.6 years ) .
serum levels of tnf- were measured by an enzyme - linked immunosorbent assay technique , using quantikine human tnf- immunoassay ( r and d system , minneapolis , mn , usa ) .
standards and samples are pipetted into the wells and any tnf- present is bound by the immobilized antibody . after washing away any unbound substances , an enzyme - linked polyclonal antibody specific for tnf-
is added to the wells . following a wash to remove any unbound antibody - enzyme reagent ,
a substrate solution is added to the wells and color develops in proportion to the amount of tnf- bound in the initial step .
the test distribution was done by kolmogorov - smirnov test , and comparisons were performed by t - test .
the study group comprised of 60 ( 36 females and 24 males ; the mean age was 35.6 years , ranging from 5 to 69 years ) patients with aa and 20 healthy controls ( 11 females and 9 males ; the mean age 32.6 years , ranging from 6 to 63 years ) .
there were no significant difference in age and female / male ratio between the patients and controls ( p > 0.05 ) .
the mean duration of aa was 14.5  25.4 ( range , 1 - 119 months ) . in the total of patients with aa , 46 of them were laa and 14 were at , au , or at / au group .
serum tnf- levels ranged from 8.8 to 17.0 pg / ml , with the highest values observed in the au patients .
the mean serum tnf- in aa patients was 10.31  1.20 pg / ml ( mean  sd ) , whereas that of laa or extensive ( at , au , or at / au ) was 10.16  0.79 pg / ml or 10.40  1.03 pg / ml , respectively .
patients with longer duration of the disease had higher concentration of tnf- , but not significantly [ figure 1 ] .
correlation between the duration of the aa and concentration of tnf-,r = 0.034 ;  ( rho ) = 0.1142 ; 95% ci ( -0,144 ; 0,358 ) ; p > 0.05;-n.s serum levels of tnf- in patients with aa were significantly higher than those in controls ( p = 0.044 ) .
there was no significant difference in levels of tnf- between patients with laa and the extensive group ( p=0.2272 ) .
serum concentrations ( meansd ) of tnf- in patients with aa , laa , at / au and in healthy controls
recent progress in the understanding of aa has shown that the regulation of local and systemic cytokines plays an important role in its pathogenesis .
hair loss may occur because proinflammatory cytokines interfere with the hair cycle , leading to premature arrest of hair cycling with cessation of hair growth .
this concept may explain typical clinical features of aa such as a progression pattern in centrifugal waves and spontaneous hair regrowth in concentric rings , suggesting the presence of soluble mediators within affected areas of the scalp .
tnf- is a multifunctional proinflammatory cytokine which has been implicated in the pathogenesis of many infections and inflammatory disorders .
however , this cytokine not only acts as mediator of immunity and inflammation , but also affects not - immune responses within tissues such as cell proliferation and differentiation . in vitro studies have shown that tnf- , along with il-1 and il- , causes vacuolation of matrix cells , abnormal keratinization of the follicle bulb and inner root sheath , as well as disruption of follicular melanocytes and the presence of melanin granules within the dermal papilla .
experiments in cultured human hair follicles by hoffmann et al . showed that tnf- completely abrogated hair growth .
additionally , tnf- induced the formation of a club - like hair follicle , similar to catagen morphology of the hair bulb .
a study by thein et al . examined cytokine profiles of infiltrating activated t - cells from the margin of involved aa lesions .
it was found that t - cell clones from involved lesions inhibited the proliferation of neonatal keratinocytes . in examining the cytokine profiles and relating them to regulatory capacity
, the authors found that t - cell clones that released high amounts of ifn- and/or tnf- inhibited keratinocyte growth .
a limited number of studies in the literature have evaluated the serum levels of tnf- in patients with aa .
the results presented in our study demonstrate that the mean serum levels of tnf- were significantly elevated in aa patients in comparison with healthy subjects .
there was no significant difference in levels of tnf- between patients with laa and the extensive group .
in contrast to our results , teraki et al . reported that serum levels of tnf- in patients with laa were significantly higher than those in patients with au . in the study of koubanova and gadjlgoroeva , serum levels of tnf- in patients with aa
did not differ from that in controls . however , tnf- was lower in patients with severe form of aa than in patients with mild form .
they hypothesized that similar levels of tnf- in patients with both forms of aa and controls may indirectly indicate the absence of systemic immunopathological reactions in patients with aa , and the lowering of tnf- level in the mild form may indicate the tendency to formation of immunodeficiency in patients with severe aa .
in addition , lis et al . found that serum levels of stnf- receptor type i were significantly elevated in patients with aa in comparison with healthy subjects . as they conclude , these results indicate that immune mechanisms in aa are characterized by activation of t - cells and other cells , possibly keratinocytes .
tnf- seems to be a useful indicator of the activity of aa and that it may play an important role in the development of this disease .
further investigations are required to clarify the pathogenic role and clinical significance of tnf- and these findings may provide important clues to assist in the development of new therapeutic strategies for patients with aa .
 background : alopecia areata ( aa ) is a common form of localized , nonscarring hair loss . it is characterized by the loss of hair in patches , total loss of scalp hair ( alopecia totalis , at ) , or total loss of body hair ( alopecia universalis , au ) . the cause of aa is unknown , although most evidence supports the hypothesis that aa is a t - cell - mediated autoimmune disease of the hair follicle and that cytokines play an important role.aims:the aim of the study was to compare the serum levels of tumor necrosis factor - alpha ( tnf- ) in patients with aa and the healthy subjects and also to investigate the difference between the localized form of the disease with the extensive forms like at and au.materials and methods : sixty patients with aa and 20 healthy controls were enrolled in the study . 
 forty - six patients had localized aa ( laa ) , and 14 patients had at , au , or at / au . 
 the serum levels of tnf- were measured using enzyme - linked immunoassay techniques.results:serum levels of tnf- were significantly higher in aa patients than in controls ( 10.31  1.20 pg ml vs 9.59  0.75 pg / ml , respectively ) . 
 there was no significant difference in serum levels of tnf- between patients with laa and those with extensive forms of the disease.conclusion:our findings support the evidence that elevation of serum tnf- is associated with aa . 
 the exact role of serum tnf- in aa should be additionally investigated in future studies . 
Introduction
Materials and Methods
Results
Discussion
Conclusion