Selective histone deacetylase-6 inhibition attenuates stress responses and prevents immune organ atrophy in a lethal septic model.

摘要: Background An overproduction of corticosterone during severe sepsis results in increased apoptosis immune cells, which may result relative immunosuppression and an impaired ability to fight infections. We have previously demonstrated that administration tubastatin A, a selective inhibitor histone deacetylase-6 (HDAC6), improves survival lethal model cecal ligation puncture (CLP) mice. The purpose this study was characterize the effects treatment on sepsis-induced stress responses function. Methods C57BL/6J mice were subjected CLP, 1 hour later given intraperitoneal injection either A dissolved dimethyl sulfoxide (DMSO), or DMSO only. Blood samples collected measure levels circulating adrenocorticotropic hormone (ACTH). Thymus long bones (femur tibia) hematoxylin eosin staining, immunohistochemistry utilized detect cleaved-caspase 3 splenic follicles as cellular apoptosis. Results All vehicle-treated CLP animals died within 3 days, displayed decreased ACTH compared with sham-operated group. These also developed atrophy thymic cortex marked depletion thymocytes. Tubastatin significantly attenuated abnormalities. Treated had lower percentages (95.0 ± 5.0 vs 42.5 25.3; P  = .0366), bone marrow (58.3 6.5 25.0 14.4%;  = .0449), (41.2 3.7 28.5 4.3 per 40× field;  = .0354). Conclusion Selective inhibition HDAC6 septic associated significant blunting responses, atrophy, Our findings identify novel mechanism behind advantage seen treatment.