Effect Of Dexamethasone On CD11b~+Gr-1~+ Myeloid-derived Suppressor Cells(MDSCs) In Septic Mice Models

Backgroung: Sepsis is systemic inflammatory response syndrome caused by an infection. myeloid-derived suppressor cells(MDSCs) are a heterogenous population of myeloid cells and possess strong immunosuppressive activities.Lowdose ofglucocorticoid(GC)is effective for reducing the organ damage caused by sepsisand reflected by the current Surviving Sepsis Campaign guidelines.There is no report about the effect of glucocorticoid on the production and accumulation of MDSCs in the process of sepsis. To investigate the influence of dexamethasone on CD11b+Gr-1+myeloid-derived suppressor cells(MDSCs) induced by lipopolysaccharide(LPS)in septic mice. we conducted the study.Objective:To investigate if low dose of dexamethasone has the influenceon CD11b+ Gr-1+myeloid-derived suppressor cells(MDSCs) induced by lipopolysaccharide(LPS) in septic mice. Methods: 145 BALB/c mice weredivided into three groups randomly, including normal controlgroup(NC group), sepsis group(SEgroup), sepsis plus low dose dexamethasone group(SDgroup).SE group and SD group were administrated 10mg/kg LPS. 2 hours after the administrated LPS, the SD group were given Dex 0.3mg/kgintravenously.the time at the end of the LPS injection was recorded as 0 hthen 6 mice from each group were selected randomly at 6h, 12 h, 24 h, 48 h, and 72 h respectivelyand were killed after anesthesia to get the splenic and bone marrow single cell suspension. anti-mouse PE-Gr-1 antibody and anti-mouse FITC-CD11 b antibody added into splenic and myeloid single cell suspension then were detected by flow cytometry to get the percentage of MDSCs in splenic and myeloid single cell suspension.while the blood collected were processed to collect serum. Serum levels of IFN-γand IL-10 of the micewere measured with ELISA kits according to the manufacturer’s instructions. 24 hours after administrated LPS, histopathological changes of the lung,liver and kindney were determined by HE staining, and then optic microscope was used for the pathological examination. The statistical analyses were done with the statistical software.Results:1.Compared with NC group, the level of IFN-γ at 6 hours and the level of IL-10 at 12hours of SE group and SD group increased significant(P<0.05~P<0.01), and there was a statistical difference between SE group and SD group(P<0.05). Compared with NC group,the percentage of MDSCs in spleen of SE group increased significant at12 to 72 hours( P < 0.01),and the percentage of MDSCs in spleen of SD group increased at 12 to 48 hours( P < 0.01),Moreover, there was a statistical difference between SE group and SD group at 24 to 72 hours(P < 0.01).Compared with NC group,the percentage of MDSCs in bone marrow of SE group and SD group increased significant at 48 to 72 hours(P<0.01 å'Œ P<0.05~P<0.01),Moreover, there was a statistical difference between SE group and SD group at 48 to 72 hours(P<0.05).2.The pathological score of acute liver, lung, and kidney damage in the SD group was significantly lower than in the SE group(P<0.01).Conclusions: The the percentage of MDSCs in spleen and bone marrow in the SD group was lower than the percentage in the SE group and there were statistically significant between them.Our results showed low dose of dexamethasone inhibited the production and accumulation of MDSCs induced by LPS in septic mice.