Inhibition of XXXX restores innate immune cells in bone marrow in a lethal septic model.

@entity19 @entity52088 @entity2091 @entity3733 @entity37871 @entity1588 @entity60192 @entity2823 @entity3804
BACKGROUND: We have previously demonstrated that @entity52088 , a selective inhibitor of histone deacetylase (HDAC) 6, improves survival, and increases circulating monocyte count and bacterial clearance in a lethal model of @entity1588 ( @entity1588 ) in @entity19 . The aim of the present study was to characterize the effects of inhibition of @entity60192 on the bone marrow cell population. METHODS: C57BL/6J @entity19 were subjected to @entity1588 , and 1 h later given an intraperitoneal injection of either @entity52088 (70 mg/kg) dissolved in @entity3733 ( @entity3733 ), or @entity3733 alone (n=9/group). Sham-operated animals were treated in an identical fashion, without @entity1588 . Forty-eight hours later, bone marrow cells were flushed out from the femurs and @entity2091 . Erythrocytes were lysed, and a single-cell suspension was made for analysis. Cells were washed, blocked with anti-mouse @entity37871 /32, stained with anti-mouse B220 PE-Cy7, CD3 APC-eFluor   780, @entity3804 @entity2823 , Gr-1 PerCP-Cy5.5 and F4/80 Antigen APC, and subjected to flow cytometry. Data was acquired on an LSRII Flow Cytometer (BD Biosciences) and analyzed with FlowJo (Flowjo, LLC). RESULTS: In comparison to the sham group, @entity1588 animals showed decreased percentage of innate immune cells ( @entity3804 +; 62.1  3.1 vs. 32.9  4.9%, p=0.0025) and macrophages ( @entity3804 + F4/80+; 44.6  3.4 vs. 19.8  2.6%, p=0.0002), and increased percentage of T lymphocytes (CD3+; 1.1  0.2 vs. 3.3  0.4%, p=0.0082) in the bone marrow 48 h after @entity1588 . Treatment with @entity52088 restored the innate immune cells (32.9  4.9 vs. 54.0  4.1%, p=0.0112) and macrophages (19.8  2.6 vs. 47.1  4.6%, p=0.0001), and increased the percentage of neutrophils ( @entity3804 + Gr-1+; 28.4  3.9 vs. 48.0  4.0%, p=0.0075). The percentages of B (B220+) and T lymphocytes were not significantly altered by @entity52088 , compared to the vehicle-treated @entity1588 animals. CONCLUSIONS: Selective inhibition of @entity60192 in this lethal septic model restored the innate immune cell and macrophage populations, and increased the neutrophil composition in the bone marrow. These results may explain the previously reported beneficial effects of @entity52088 treatment in a septic model. LEVELS OF EVIDENCE: not applicable (animal study).
