| Objective: To investigate the clinical effectiveness of high-dose dexamethasone (HDDex) combined with thymosin α 1( T α 1) therapy in patient with chronic idiopathic thrombocytopenic purpura (ITP).Materials and Methods: 52 ITP patients (18 males and 34 females, median age 39 years; range, 18-83 years) were studied. The patients' platelet(Plt) count ranged from 1×10~9/L to 58×10~9/L, median count was 14×10~9/L. A total of 10 normal controls were measured for T α 1, including 4 males and 6 females, aged 22-51 years (median age 31 years), Plt count ranged between 124×10~9/L and 278 ×10~9/L(median 188×10~9/L). All of the plasma samples were isolated from 4 ml EDTA-anticoagulated peripheral blood by centrifuging at 2000 rpm at room temperature for 20min, and then stored at -20℃ for future use. The follow-up periods ranged from 1 to 36 months, median time was 6 months, the plasma samples were obtained before and 1 month after therapy. The plasma level of T α 1 were measured by ELISA. Treatment protocol: dexamethasone 40mg/d was administered orally for 4 consecutive days; thymosin α 1 1.6mg was subcutaneously injected three times a week, for 4 weeks. The datas were expressed as mean±standard deviation(M±SD), and unpaired Students' t-test between two groups and paired t-test between samples before and after treatment were performed; the rates contrast were performed by Fisher exact Chi square test. All tests were performed by SAS system.Results: (1)The result of plasma level of T α 1 in ITP patients was 2.43±1.47 ng/ml and significantly higher than normal controls( 1.77 ±0.69 ng/ml, P < 0.05). T α 1 plasma level of 19 cases of ITP patients before and after HDDex / T α 1 therapy was 2.52±1.36ng/ml and 2.14±1.02 ng/ml, respectively, though the difference was not significant (P > 0.05), T a 1 plasma level of treated group almost declined to the normal range(P > 0.05). ?The short term efficacy of all patients was 100%(complete response, partial and minimal response rate was 71.15%-. 21.15% and 7.69%, respectively) by HDDex / T a 1; it was also promising with about 62% of long term response rate. But the short term complete response rate in the lower T a 1 group was relatively higher than the higher group (78. 13%vs 60.00%, P > 0.05) , and there was also higher long term complete remission rate in the lower T a 1 group(48.21% vs 31.25%, respectively), and the long term therapeutic response rate of both groups was 65.45% and 56.25%, respectively(/) > 0.05) during follow-up period, although differences were not significant. ?Side effects: there were no serious side effects of glucocorticosteroids occurred such as metabolized abnormality of multiple systems , agitated and with drawal symptoms during short term Dex therapy; insomnia occurred only in some patients, therefore all cases had been finished therapy.Conclusion: CD Plasma level of thymosin a 1(T a 1) in ITP patients was significantly higher than normal controls. This observation implicate self-regulation mechanism of thymus induced by abnormal cellular immunity. T a 1 plasma level of ITP patients after HDDex / T a 1 therapy was declined to the normal range, indicating that HDDex / T a l could down-regulate the T a 1 level of ITP patients. ?The short term efficacy of both the higher and the lower T a 1 level groups was 100%; but the complete response rate in the latter group was higher, and there was also higher complete remission rate in the lower T a 1 group during follow-up period, although difference was not significant. Further study with more cases is warranted. ?The HDDex / T a 1 showed high response rate and few serious side effects; it was also promising with about 62% of long term response rate and low relapse rate without maintaining therapy. All datas showed superiority of HDDex / T a 1 over conventional therapy for patients with ITP.Objective: To study cellular immunity in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) via investigation of changes of plasma cytokines profiles of Thl, Th2 and Th3 T cells before and after high-dose dexamethasone(HDDex) combined with thymosin a 1(T a 1) therapy, and to comprehend the therapeutic mechanism in cellular immune function, so as to guide the clinical intervention of the disease.Materials and Methods: 52 ITP patients(18 males and 34 females, median age 39 years; range between 13 and 83 years) were studied. The patients' platelet(Plt) count ranged from 1 X 109/L to 58 X 109/L, median count was 14 X 109/L. A total of 10 normal controls were included( 4 males and 6 females, aged from 22 to 51 years, median age 31 years, Pit count ranged from 124X107L to 278X107L, median amount 188X 107L). All of the plasma samples were isolated and stored as part I . The follow-up periods ranged from 1 to 36 months, median time was 6 months. Plasma samples were also obtained 1 month after therapy. The plasma level of all cytokines were measured by ELISA. Treatment protocol: dexamethasone 40mg/d was administered orally for 4 consecutive days; 1.6mg of thymosin a 1 was subcutaneously injected three times a week, for 4 weeks. The datas were expressed as mean± standard deviation(M±SD), and unpaired Students' t-test between two groups and paired t-test between samples before and after treatment were performed; and relationship between T a 1 and every Th cytokine after dexamethasone / thymosin a 1 therapy were performed by linear regression analysis. All tests were performed by SAS system.Results: (Din ITP patients with active disease, the plasma levels of both IFN- Y and IL-2 were significantly increased (22.71±7.98 pg/ml and 28.42±11.27 pg/ml,respectively) compared with the normal controls(10.23±3.97 pg/ml and 8.73±8.22 pg/ml, P < 0.01, respectively); after HDDex / T a 1 management, both of IFN- Y and IL-2 had a significantly decrease (11.57± 4.33 pg/ml and 14.56±10.76 pg/ml, P < 0.01, respectively) compared with the untreated patients. After treatment, both of the two cytokines were normalized as compared with the normal controls (P > 0.05, respectively).?On the contrary, both IL-4 and IL-10 in ITP patients with active disease had significantly decreased levels (5.93±3.85 pg/ml and 3.24±1.36 pg/ml, respectively) compared with the normal controls (14.39±8.03 pg/ml and 8.67±3.04 pg/ml, P < 0.01, respectively); however, both of IL-4 and IL-10 had a significantly increase (9.87± 4.82 pg/ml and 7.90±2.71 pg/ml, P < 0.01, respectively) after management. There were no significant differences between treated patients and normal controls in both IL-4 and IL-10 levels (P > 0.05, respectively) .(3)TGF- P 1 levels in active ITP patients had a significantly decrease ( 1.31 ±0.71 ng/ml) compared with the normal controls(7.87± 2.54ng/ml, P < 0.01); after management, TGF- P 1 significantly increased to 4.19+1.80 ng/ml (P < 0.01) , but still lower than the normal controls (P < 0.05) .?In 19 cases of patients after HDDex / T a 1 treatment, none of significantly correlation was found between T a 1 plasma level and IFN- y or IL-2 or IL-4 or IL-10 level (P > 0.05), but there was significantly positive correlation between T a 1 level and TGF- 3 1 level(P < 0.01). ?As a regulating factor of megakaryocytopoiesis, TPO plasma levels in ITP patients with active disease had no significant changes as compared with treated patients and normal controls (77.89 + 29.71 pg/ml, 57.77 + 32.44 pg/ml and 58.41 + 26.55 pg/ml, respectively, P > 0.05); however, as another regulating factor, IL-11 in patients with active ITP showed a significantly increased level compared with the normal controls (126.74±44.23 pg/ml and 31.19 + 9.20 pg/ml, respectively , P < 0.01), after management, IL-11 significantly declined to 76.12 + 51.27 pg/ml (P<0.05) ,but still higher than the normal controls (P < 0.05) .Conclusion: ?Our results support that ITP is a kind of autoimmune disease with Thl cells having predominant functions. The Thl shift can be corrected by T a 1 combined with Dex therapy, implicating a dysfunctional cellular immunity in thepathogenesis of ITP, and a potential target for novel intervention. (2)As a specific phenotype of Th3 cells, TGF- P 1 levels showed a significantly positive correlation between T a 1 level and TGF- P 1 level after therapy, indicating the induction of physiologic immunosuppresive effect of NK cells and the autoimmune tolerance by T a 1 combined with Dex. (3)As regulating factors of megakaryocytopoiesis, our data suggest that the numbers of circulating Pits may not the sole regulator of endogenous TPO level, other Mpl-expressing cells of the megakaryocyte lineage may also contribute to the regulation of circulating TPO level; but IL-11 levels may in part be regulated by a negative feedback loop based on circulating Pit numbers, also may be regulated by a variety of inflammatory stimulant factors.
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