Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018133 (
graft-versus-host disease
)
18,032
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Graft-versus-host disease
(
GVHD
) is the major complication after allogeneic bone marrow transplantation.
Valproic acid
(
VPA
) was described as a histone deacetylase inhibitor that had anti-inflammatory effects and reduced the production of proinflammatory cytokines in experimental autoimmune disease models. Using well-characterized mouse models of MHC-mismatched transplantation, we studied the effects of
VPA
on
GVHD
severity and graft-versus-leukemia (GVL) activity. Administration of
VPA
significantly attenuated the clinical severity of
GVHD
, the histopathology of
GVHD
-involved organs, and the overall mortality from
GVHD
.
VPA
downregulated Th1 and Th17 cell responses and cytokine production in vitro and in vivo, whereas its effect on
GVHD
was regulatory T cell independent. The effect of
VPA
was related to its ability to directly reduce the activity of Akt, an important regulator of T cell immune responses. Importantly, when mice received lethal doses of host-type acute leukemia cells, administration of
VPA
did not impair GVL activity and resulted in significantly improved leukemia-free survival. These findings reveal a unique role for
VPA
as a histone deacetylase inhibitor in reducing the donor CD4(+) T cells that contribute to
GVHD
, which may provide a strategy to reduce
GVHD
while preserving the GVL effect.
...
PMID:Valproic Acid Ameliorates Graft-versus-Host Disease by Downregulating Th1 and Th17 Cells. 2617 2
