| BackgroundGraves disease (GD) is an autoimmune disease, which pathogenesis has not yet been fully elucidated. The balance disorders of Helper T lymphocytes (Thl) and helper T cell 2 (Th2) play a key role in the occurrence, development and prognosis of GD. Most people thought the immune response of GD was related to humoral immunity(Th2-type response ), but recent studies have indicated that cellular immunity (Th1-type response) also play an important role in the pathogenesis of GD, which absorbed more attention. 131I therapy, safe, effect, convenient, is more and more used for clinic. As an radioactive nuclide, theβ-ray released from 131I can destroy the thyroid follicle, decrease the volume of thyroid, inhibit the generation of thyroid hormones, to reach the goals of treatment. Because T cell is more sensitive to the radiation, 131I therapy have lethal effect on the infiltrative lymphocytes of the thyroid, which can induce the resistance mechanism disorders. A large number of studies have shown that a variety of cytokines involved in the imbalance of the immune regulatory networks, and the conclusions are different, but the conclusion of the study in Interleukin-6 were similar. Chemokines, mainly induced by active T cells, mononuclear cells and tissue cells, belonging to a kind of inducible, secreted pre-inflamatory, and regulating directional migration of different immune cells and interaction. In recent years, overseas study found that CXCL10, correlated with Th1 immune response, may involved in the pathogenesis of GD, and to reread normal with the immune remission after treatment. The injuries of immunopathogenesis in GD is actually a process of inflammatory reaction, the physical injury of thyroid follicular cell, caused by 131I therapy, may aggravate the immune inflammatory reaction, but the exact mechanism is unclear, in the early stage of 131I therapy in GD, particularly the 1～2 months, the research reports about the changes of serum CXCL10 and IL-6 were much less.ObjectiveObserve the levels of serum CXCL10, IL-6, FT3, FT4, TSH and TPOAb in patients of Graves disease (GD) before and after 1 week, 2 weeks, 2 months of 131I treatment. Observing the changes of CXCL10 and IL-6 levels in the early stage of 131I therapy, analyzing their correlation with FT3, FT4, TSH, TPOAb, age and the duration of disease. judgmenting the early inflammatory response of thyroid after 131I therapy, in order to understand the recovery of immune function after 131I therapy.MethodsCollecting a total of 43 subjects with GD of Endocrinology of Linyi People's Hospital, all the subjects were in hospital from Sep 2009 to May 2010 who receiving the treatment of 131I. aged 20-57 years, the mean age was (35.88±9.79) years, including 9 males, aged 23-50 years whose mean age was (34.56±10.19) years; 64 females, aged 20-57 years whose mean age was (36.24±9.81) years. The duration of disease was from 2 weeks to 2 years which average was 6.06 months. In the case group, there were 9 patients with thyroid associated ophthalmopathy,including 3 males and 6 females, which mean age was (36.78±10.47) years. The diagnosis of GD hyperthyroidism was established on the basis of China 2008 Graves disease diagnostic criteria of Guide to Diagnosis and Treatment of thyroid diseases in China, and excluded Hashimoto thyroiditis (HT), subacute thyroiditis, iatrogenic hyperthyroidism, secondary hyperthyroidism, hyperthyroidism during pregnancy and so on. All the GD patients with hyperthyroidism have not used anti-thyroid drugs (ATD), glucocorticoids and other immunosuppressive therapy, without other autoimmune diseases, infectious diseases and so on. Select 30 case from Linyi People's Hospital over the same period who having health examination as a control group, whose thyroid function was normal, negative for thyroid autoantibodies. excluding of thyroid disease, liver disease, diabetes mellitus and autoimmune history and family history of thyroid disease, and no infection within the past one month. The control group included 7 males and 23 females, aged 22-54 years, the mean age was (36.28±7.26) years, sex, age and patient group were comparable. The gender and age of each groups were comparable.Results1. The results of serum FT3,FT4,TSH and TPOAb in GD patientsBefore 131I treatment, the levels of serum FT3, FT4 and TPOAb in GD patients were significantly higher than the control group (P <0.01); the levels of serum TSH was significantly lower than the control group (P <0.01). After one months of 131I treatment, the levels of serum FT3 and FT4 in GD patients were significantly lower than the control group(P<0.05), but still higher than the control group (P <0.05), the levels of serum TSH was lower than before treatment and the control group (P <0.05), compared with pre-treatment, there was no statistically significant of the levels of serum TPOAb (P> 0.05). After two months of 131I treatment, the levels of serum FT3 and FT4 were significantly lower than pre-treatment and two months treatment (P <0.05); the levels of serum TSH was significantly higher than pre-treatment and two months treatment (P <0.05), but there was no statistically significant compared with control group; the levels of serum TPOAb were significantly higher in patients before treatment and 1 month after treatment (P <0.05) (Table 2, Table 3).2. The results of serum CXCL10 and IL-6 in GD patientsBefore 131I treatment, the levels of serum CXCL10 and IL-6 in GD patients were significantly higher than the control group (P <0.01), and significantly higher than pre-treatment after one week of 131I treatment, lower than pre-treatment and 2 weeks of 131I treatment, but still higher than control group, and all the differences had statistically significant(P <0.01) (Table 2, Table 4).3. The results of serum CXCL10 and IL-6 Graves ophthalmopathy(GO) and no-ophthalmopathyBefore 131I therapy, the levels of serum CXCL10 and IL-6 in Graves ophthalmopathy were significantly higher than in patients with no-ophthalmopathy and control group, after one week, two weeks and two months of 131I therapy, the changed tendency were similar with case group, but the extents were significantly higher than in patients with no-ophthalmopathy (Table 5).4. The correlation between serum CXCL10, IL-6 and FT3, FT4, TSH, TPOAb, age, the duration of diseaseRespectively defining the serum CXCL10 and IL-6 as the dependent variable, FT3, FT4, TSH, TPOAb and age, duration as the independent variable. Using the multiple linear correlation analysis to observe the correlation. The results showed that there were no correlation about the serum levels of CXCL10 in patients with GD hyperthyroidism and FT3, TSH, TPOAb, age, duration(r = 0.044,0.035,0.181,0.003,0.04; P> 0.05); serum CXCL10 had correlation with FT4(r = 0.336, P = 0.03). The levels of serum IL-6 had no correlation with FT3, FT4, TSH, TPOAb and age, disease duration (r = 0.265,0.213, -0.024,0.168, -0.229,0.073; P> 0.05) (Table 6, Table 7).ConclusionsIn our research, we found that the levels of serum CXCL10 and IL-6 were significantly increased before 131I treatment, and were slightly higher than pre-treatment after one week of 131I treatment, and were significantly lower than pre-treatment and after 1 week treatment. Serum CXCL10 may be involved in the pathogenesis of GD hyperthyroidism. We can comprehend the early inflammatory response and the recovery of immune function and provide reference for clinical treatment according to observe the dynamic changes of serum CXCL10 and IL-6 after 131I treatment in GD patients with hyperthyroidi sm. |
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