| Objective: CXCL10 is an important chemokine which belongs to the family of ELR-CXC chemokine, also called INF-γ-inducible Protein 10(IP-10) is a protein which can induced by interferon- (IFN) -γduring inflammation and display potent lymphocyte chemotactic activity. CXCL10 was found to bind a receptor named as CXCR3 (Antibody to CXC Chemokine Receptor 3), and can take chemotactic activity on different cells types of the immune system. In particular, activated T cells, B cells, macrophages, and NK cells have been found to express CXCR3 and can be attracted in inflamed tissues. CXCL10 is a very important cytokine in many diseases .CXCL10 can mediated Th1-mediated immune responses, actived histoleucocyte and T-cell, associated with metaphysis immunogenesis and autoimmune disease. CXCL10 not only mediates leukocyte recruitment, but also drives T-cell proliferation to allogenic and antigenic stimulation, and IFN-γsecretion in response to antigenic challenge. Accordingly, CXCL10 up-regulates the production of Th1 cytokines and downregulates the production of Th2 cytokines. The major function of CXCL10 is the recruitment of leucocytes to inflammation sites, but they also play a role in tumoral growth, angiogenesis and organ sclerosis. Graves' disease(GD)is a common organ-specific autoimmune disease. Graves'disease, which causes only hyperthyroidism, or Graves' Ophthalmopathy (GO) with euthyroid, and hyperthyroidism with GO. Graves' disease involving the production of thyrotropin (TSH) receptor (TSHR) antibodies (TRAb), which overstimulate thyroid cells to result in hyperthyroidism. Its pathogenesis hasn't been completely clarified until now. Recent years, chemokines played an important role in Graves' disease. We want to examine the serum levels of CXCL10 in patients with Graves' disease, and to explore the probable action of CXCL10 in Graves' disease. Thus we can provide a new experimental evidence for explaining the pathogenesis of human Graves' disease.Methods: we divide 75 patients with Graves' disease into three groups :(1) Untreated group: 30 patients at the time of diagnosis.(2) Euthyroid group: 25 patients with euthyroid after regular treatment with antithyroidism drugs(The symptoms disappear obviously, the levels of FT3, FT4, TSH are normal).(3) Relapsed group: The patients with Graves' disease who have been treated for one and a half years at least and relapse after drug withdrawal.total 20. And there also have 25 samples age and sex matched healthy subjects served as control. Their morning fasting 5ml blood samples were collected from elbow vein. The levels of FT3, FT4, TSH, TPOAb and TGAb are measured with chemiluminescence. We also examined the serum levels of CXCL10, thyrotrophin receptor antibody thyroid (TRAb) and stimulating antibody (TSAb) by enzyme linked immunosorbent assay (ELISA). All the data were analyzed by statistical software spss10.0 version.The significance was indicated by P value, the difference which had the significance was indicated by P<0.05.Results:1 Serum levels of FT3, FT4, TSH in various groups The serum levels of FT3 and FT4 were significantly higher in untreated group(23.88±5.69,88.35±35.27 pmol/L) and relapsed group(19.49±7.59,62.07±37.49 pmol/L) than those in euthyroid group(4.32±0.47,18.89±6.78 pmol/L) and control group(5.80±0.64pmol/L,19.97±3.72 pmol/L). The differences were significant (P<0.01). The serum levels of TSH were lower in untreated group (0.0089±0.014 mIU/ml) and relapsed group (0.0049±0.0035uIU/L) compared with euthyroid group (1.54±0.99 mIU/ml) and control group (1.67±1.07mIU/ml), the differences were significant (P<0.01) there was no significant difference between the latter two groups (P>0.05).2 Serum levels of TPOAb and TGAb in various groupsThe serum levels of TPOAb and positive rate were significantly higher in untreated group, relapsed group and euthyroid group compared with control group ( TPOAb: 194.52±151.32 pmol/L,56.7%; 198.96±128.78 pmol/L,60%; 192.34±135.46 pmol/L,44 %VS 70.88±57.69 pmol/L, 8%), the differences were significant (P<0.01). There was no difference among the prec three groups (P>0.05). The serum levels of TGAb and positive rate were significantly higher in untreated group, relapsed group and euthyroid group compared with control group ( TGAb: 181.67±121.80 pmol/L,46%; 215.24±135.37 pmol/L,48%; 209.34±118.56 pmol/L, 55%VS 52.77±42.46 pmol/L,4%) , the differences were significant (P<0.01).There was no significant difference between the prec three groups (P>0.05).3 Serum contents of TRAb and TSAb in varoius groupsThe serum levels of TRAb and positive rate in patients of untreated group, relapsed group and euthyroid group (1.27±0.27,76.7%;1.28±0.24,80%;1.07±0.24,52%) were higher than control group (0.85±0.16,0%) , the differences were significant (P<0.01). The serum levels of TRAb and positive rate in patients of untreated group and relapsed group were higher than euthyroid group, the differences were significant (P<0.05).There was no significant difference between untreated group and relapsed group group (P>0.05). The serum levels of TSAb and positive rate in patients of untreated group (1.16±0.33,76.7 % ) and relapsed group (1.19±0.39,75%) were higher than those of control group (0.84±0.21,0%), the differences were significant (P<0.01), and euthyroid group (0.98±0.29,40%), the differences were significant (P<0.05) .There was significant difference between euthyroid group and control group in the serum levels of TSAb (P<0.05) and positive rate (P<0.01). There was no significant difference between untreated group and relapsed group (P>0.05).4 Serum contents of CXCL10 in varoius groupsThe serum levels of CXCL10 in patients of untreated group (7.87±0.84ng/ml) and relapsed group (6.57±1.53ng/ml) were higher than those of euthyroid group (2.91±0.55ng/ml) and control group (3.00±0.57 ng/ml). The diffrence was significant (P<0.01).There was no significant difference between euthyroid group and control (P>0.05). The serum levels of CXCL10 in patients of untreated group were higher than relapsed group. The diffrence was significant (P<0.01)5 Correlation of serum CXCL10, FT3, FT4, TSH, TPOAb, TGAb, TRAb and TSAbThe serum levels of FT3 and FT4 correlated positively with CXCL10 ( r was 0.83 and 0.79 ,respectively, P<0.01) correlated negatively with TSH ( r=-0.66,P<0.01).In contrast,the serum contents of CXCL10 didn't correlated with TPOAb,TGAb. ( r was 0.18,0.19, respectively, P>0.05).The serum levels of CXCL10 didn't correlated with TRAb and TSAb. (r was 0.16,0.18,respectively,P>0.05). TRAb and TSAb didn't correlated with FT3, FT, TSH (r was 0.17,0.16,-0.21;0.20,0.18,-0.19, respectively,P>0.05). TPOAb and TGAb didn't correlated with FT3, FT4, TSH (r was 0.15,0.05,-0.18 ;0.19,0.09,-0.18,respectively,P>0.05).Conclusion: The serum levels of CXCL10 in patients of untreated group and relapsed group were significantly high, especially in untreated group, after modulation by antithyroid drug therapy, with a decrease in the serum levels of CXCL10 until reaching euthyroidism, and demonstrate a strong association with the level of FT3, FT4, TSH. CXCL10 is a significant influencing factor with FT3, FT4, TSH. The serum levels of FT3, FT4, TSH didn't correlated with TPOAb, TGAb, TRAb and TSAb, and the serum levels of CXCL10 didn't correlated with TPOAb, TGAb, TRAb and TSAb either, demonstrating that the CXCL10 is specifically associated with immunologic abnormality in Graves'disease. CXCL10 as a very important chemokine, CXCL10 serum levels can as a prognostic marker in patients treated with antithyroid drug or after achievement of remission and might provide a useful parameter for the evaluation and prediction of disease activity and progression.
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