ABSTRACT
To observe the effects of hepatocyte growth factor (HGF) on graft-versus-host disease (GVHD) and Th1/Th2 related cytokines in mice with acute lymphoblastic leukemia (ALL) after allogenic bone marrow transplantation (allo-BMT), BALB/c mice were conditioned by total body irradiation with 11 Gy and then were transplanted with allogeneic bone marrow after establishing ALL model. BALB/c mice were divided into groups A and B. The mice of group A were injected subcutaneously with HGF from day 0 to 7 after allo-BMT, and the mice of group B were injected subcutaneously with PBS from day 0 to 7 after allo-BMT. The symptoms of GVHD and the GVHD pathological changes of liver and small intestine and skin were observed. The serum levels of both IFN-gamma and IL-4 were determined by ELISA. The results showed that the score of GVHD in group A was lower than that in group B (P < 0.05). The levels of IFN-gamma in both groups A and B were all higher than that in normal group (P < 0.05 and P < 0.001, respectively), However, the level of IFN-gamma in group A was lower than that in group B (P < 0.01). The levels of IL-4 in both group A and B were all lower than that in normal group (P < 0.05), but the level of IL-4 in group A was higher than that in group B (P < 0.05). It is concluded that HGF can alleviates the severity of GVHD, because of its balancing the Th1/Th2-related cytokines after allo-BMT.
Subject(s)
Animals , Female , Male , Mice , Bone Marrow Transplantation , Methods , Cytokines , Blood , Enzyme-Linked Immunosorbent Assay , Graft vs Host Disease , Allergy and Immunology , Hepatocyte Growth Factor , Pharmacology , Interferon-gamma , Blood , Interleukin-4 , Blood , Mice, Inbred BALB C , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Blood , Allergy and Immunology , General Surgery , Th1 Cells , Allergy and Immunology , Th2 Cells , Allergy and Immunology , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of hepatocyte growth factor (HGF) on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) after allogeneic bone marrow transplantation (allo-BMT) and related mechanism in acute lymphoblastic leukemia (ALL) mice.</p><p><b>METHODS</b>Twenty nude mice were randomly divided into control (group A) and test (group B) groups for monitoring relapse, and 20 BALB/c mice into control (group C) and test (group D) groups for GVHD. HGF as injected from day 0 to day 7 after BMT for groups B and D, while PBS for A and C. CD4(+) and CD8(+) T cell were evaluated by flow cytometry. The survival of mice after BMT was recorded. The level of tumor necrosis factor-alpha (TNF-alpha) was evaluated by ELISA.</p><p><b>RESULTS</b>The median past-BMT survival were 7.00 +/- 1.58, 9.00 +/- 1.58, 11.00 +/- 3.95 and 24.00 +/- 13.44 days for groups A, B, C, D, respectively, being prolonged in group D. HGF could decrease the quantity of CD4(+) T cells [group D (10.39 +/- 1.15)% vs group C (13.50 +/- 1.80)%, P < 0.01] and increase CD8(+) T cell [group D (12.25 +/- 2.85)% vs group C (6.12 +/- 1.99)%, P < 0.01], decrease the level of TNF-alpha in transplanted ALL mice [group D (112.10 +/- 18.99) pg/ml vs group C (143.90 +/- 25.35) pg/ml, P < 0.01] and reduce the degree of GVHD.</p><p><b>CONCLUSION</b>HGF could alleviate post-allo-BMT GVHD but retain GVL effect.</p>