Abstract
Objective
To evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT).
Methods Established model of allogenic murine HSCT (C57BL/6→BALB/c). The severity of acute graft-versus-host-disease (GVHD) was assessed by a clinical scoring system that incorporates five clinical parameters: weight loss, posture, activity, fur texture and skin integrity. The intra-cellular levels of interferon-γ (INFγ), tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) in thymocyte were analyzed by protein array and thymic function was evaluated by quantification of signaljoint TCR rearrangement excision circles (sjTRECs).
Results Recipients in group A (allogenic mice), B( allogenic LHRH castrated-mice) and C (syngenic mice) all attained hematopoiesis reconstitution. White blood cell counts of mice in groups A, B and C were over 1.0×109/L on day (10.60±1.34), day (9.40±0.55) and day (9.40±0.89), respectively. There was no significant difference among the time of hematopoiesis reconstitution in three groups. The time of acute GVHD occuring was on day +11±0.5 and +14±0.5 posttransplantation, respectively, in groups A and B, and all mice had acute GVHD with the incidence of 100% in groups A and B. The average scores of acute GVHD in groups A and B were (1.56±0.51) and (0.92±0.49), respectively. Acute GVHD scores in group A was significantly higher than that in group B (P=0.000). The levels of INFγ, TNFα and IL-1β in control groups were 1.67±1.76 ng/ml, 1.69±1.07 pg/ml and 5.55±3.56 pg/ml, respectively. The levels of INFγ in groups A, B and C were (10.74±2.55) ng/ml,(6.81±2.33) ng/ml and (5.52±3.96) ng/ml, respectively. The levels of TNFα were (7.51±2.89) pg/ml, (4.30±0.63) pg/ml and (3.36±2.31) pg/ml, respectively. The levels of IL-1β were (25.83±8.91) pg/ml, (19.33±3.03) pg/ml and (11.94±4.00) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P=0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those of control group (P 0.010,0.037,0.000). The levels of INFγ in group C were significantly higher than those of the control group (P=0.044). Among groups A, B and C, there were significant differences in the levels of INFγ, TNFα and IL-1β (P=0.001,0.000,0.000). The levels of INFγ and TNFα in group A were significantly higher than those in group B (P=0.041,0.013). The levels of INFγ, TNFα and IL-1β in group A were significantly higher than those in group C (P=0.009, 0.002, 0.000). The analysis of linear regression showed that the average levels of INFγ paralled with aGVHD scores (r2 0.363,P=0.038). The average sjTRECs copies/1000 PBMNCs were (39.41±44.68) in the control group and (12.29±13.02), (58.01±71.82) and (19.61±14.59) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P=0.575).
Conclusion INFγ ATNFα and IL-1β might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intracellular levels of INFγ and TNFα in thymocyte.
The Influence of the Physiotherapeutic Program on Selected Static and Dynamic Foot Indicators and the Balance of Elderly Women Depending on the Ground Stability
