Anti-Cancer Drugs Dampen Immune System

May reduce graft-versus-host disease after bone marrow transplant

MONDAY, June 23 (HealthDay News) -- Anti-tumor and anti-inflammatory inhibitors known as histone deacetylase inhibitors can dampen the immune system and reduce the incidence of graft-versus-host disease in mice after a bone marrow transplant, according to study findings published online June 20 in the Journal of Clinical Investigation.

Pavan Reddy, M.D., from the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues studied the effect of two histone deacetylase inhibitors -- suberoylanilide hydroxamic acid and ITF 2357 -- on immune cells known as dendritic cells from mice.

The researchers found that pretreating dendritic cells with the inhibitors reduced the secretion of proinflammatory cytokines and reduced the incidence of graft-versus-host disease if injected into mice after a bone marrow transplant. The effect was mediated through increased expression of a molecule called IDO, which suppressed dendritic cell function, and a lack of IDO substantially reversed many of the effects of the histone deacetylase inhibitors.

"Together, these data show that histone deacetylase inhibitors regulate multiple dendritic cell functions through the induction of IDO and suggest that they may represent a novel class of agents to treat immune-mediated diseases," Reddy and colleagues conclude.

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