Changes Of CXCL10, IL-6, ICAM-1Levels In Graves Disease Patients After¹³¹I Treatment

BackgroundGraves’ disease (GD) is an organ-specific autoimmune diseases with increasingthyroid hormone, and its pathogenesis is unclear. GD is accounting for80%ofhyperthyroidism, the prevalence in China is0.25-1.09%. The exact pathogenesis is unclear,most view is that the cytokines is related to occurrence, development, outcome andprognosis of Graves’ disease, especially Th cell proliferation and polarization anomalieslead to imbalance of Th1/Th2immune response disorder, which aggravate the immuneprocess, but the conclusion remains controversial. Most view is that the immune responseof GD was related to Th2-type response, However, recent data indicates that immune cells(Th1-type) also played a key role in pathogenesis of GD.Surgery, antithyroid drugs (ATD),131iodine is the three mainly methods of GD. Weuse131I therapy since1958in our country. It can release β-rays, induce apoptosis, causes aportion of the thyroid follicular cell membrane rupture, cell death, release of the contentsinto the blood circulation, leading to an antigen-antibody reaction. Clinicians were plaguedby the prognosis of131iodine therapy, Ahmad found that the thyroid autoantibodiesbefore GD131iodine treatment is an independent predictor of the occurrence ofhypothyroidism, Chiovad considered that failure of treatment is related to high titers ofTSAb levels before treatment, whereas the hypothyroidism is related to elevated TSAblevels after treatment. Other scholars reported that thyroid autoantibodies levels beforetreatment did not affect the incidence of hypothyroidism after131I therapy of GD patients.Visible, the prognosis of thyroid autoantibodies in GD with iodine-131therapy are notconsistent.Cytokines received more and more attention in the pathogenesis of GD. In recentyears, some abroad study showed that CXC chemokine ligand10(CXC chemokineligand-10, CXCL10) associated with the Th1immune response, resulting inhyperthyroidism in Graves’ disease after treatment with normal immune functions tend to get better. Interleukin-6(interleukin-6, IL-6) is Th2-type cytokines, through autocrine andparacrine to help proliferation and differentiation of B cells, mediating humoralimmunodeficiency reaction, the trends before and after treatment of Graves’ disease arebasically same. ICAM-1belongs to the immunoglobulin superfamily and it can mediatethe process of lymphocyte adhesion to endothelial cells and reflect the intensity of theinflammatory response. Theoretically, the trend of serum IL-6, CXCL10, ICAM-1inpatients with GD may reflect the degree and type of inflammatory response that can predictclinical outcome after131I therapy. Only a few studies have reported IL-6, CXCL10,ICAM-1dynamic changes after131I therapy.ObjectiveObserve the levels of serum CXCL10, IL-6, CXCL10/IL-6, ICAM-1in patients ofGD before and after3days,1month,2months,3months,6months,12months,18months of131I treatment. Observing the changes of CXCL10, IL-6, ICAM-1standard after131I therapy, discussing the role of CXCL10, IL-6, ICAM-1in the development of Graves’disease, judgmenting the inflammatory response of thyroid after131I therapy, exploringthese cytokines in predicting clinical outcomes in patients with iodine-131therapy.MethodsRandomly selecting newly diagnosed patients with Graves disease before receivingiodine131and after receiving iodine131treatment (the experimental group) in Linyi CityPeople’s Hospital in July2010-July2013. All subjects have not used glucocorticoids,ATD and other immunosuppressive treatment, without other infectious diseases,autoimmune diseases and so on. Collect clinical data and blood before and after three days,1month,2month,3month,6month,12month,18month after Iodine131treatment, andselact30cases who are healthy and euthyroid in the same time as a control group, andthyroid autoantibodies was feminine. Excluding of autoimmune disease, liver and diabetesdisease, and without infection in the past one month. Two groups are comparable in gender,age.Collecting fasting blood in the control group and the experimental group study of,3000r/min centrifugating15minutes, separating serum, FT3, FT4, TSH levels bychemiluminescence; measuring CXCL10, ICAM-1, IL-6by ELISA.Results1. Before131I treatment, the FT3, FT4, CXCL10, IL-6, ICAM-1levels in GD patientswere apparently higher than the control group (P <0.01); the TSH level was apparently lower than the control group (P <0.01); there is no apparent difference of CXCL10/IL-6between the control group and the case group(P>0.05).2. Comparison of CXCL10, IL-6levels before and after treatment of the GD patientsshowed significant increasion in a short period after131I therapy, then decreased graduallyafter1month, CXCL10has dropped to170.6218.25pg/ml after6months, IL-6levels hasdropped to94.447.38pg/ml after12months, both of them are lower than pre-treatment(P<0.01), then decreaseding continuing to18months, but still higher than the normal controlgroup(P <0.01)(Fig.3). CXCL10/IL-6value was significantly higher in the three daysafter131I therapy(P<0.01), then there was a downward trend, which has been lower thanpre-treatment and control group levels after1month(P＜0.05).3.ICAM-1has no significant difference3days after treatment than pre-treatmentlevels, and there was a rising trend after1month, and then continued to rising, reaching apeak after12month(P <0.001), continued to18month(P <0.01), as shown in table3.ConclusionsBefore131I therapy, CXCL10, ICAM-1, IL-6levels in experimental group wereapparently higher than the control group, suggesting that they probablely participate in themechanism of Graves’ disease. Serum levels of CXCL10and IL-6significantly increasedat day3after131I therapy, but there is a downward trend after1month, we believe thatserum CXCL10, IL-6participate in immune and inflammatory reaction after131I therapy inpatients with Graves, whose changes before and after treatment can reflect the degree ofimmune and inflammatory responses. Therefore, by dynamic monitoring of serumCXCL10, IL-6levels in patients with Graves disease after131I therapy, we can comprehendthe changes in their immune inflammatory response, predicting clinical outcome.