Effects of apilimod on steady-state hematopoiesis in mice
Objective To study the effect of apilimod on hematopoietic cells in mice under steady-state conditions.Methods 6-8-week-old male C57BL/6J mice were divided into the solvent control group(vehicle)and apilimod administration group,which were intraperitoneally injected with the vehicle and apilimod 0.2 mL/mouse,respectively.Before and after administration,peripheral blood cell counts,the absolute value of hematopoietic stem and progenitor cells from peripheral blood/spleen/bone marrow and the concentrations of such cytokines as IL-10 in serum were compared between the two groups.In the hematopoietic stem progenitor cell detection experiment,a plerixafor(AMD3100)group and water for injection(WFI)control group were set up,which were injected with AMD3100 at 5 mg/kg and WFI 0.2 mL/mouse,respectively.Results The peripheral blood cell count of mice changed significantly at 6-12 h after a single intraperitoneal injection of apilimod 40 mg/kg,but returned to the pre-administration level at 24 h post-treatment.At 9 h after apilimod injection,the number of platelets of mice treated with apilimod was 78.2%of the pre-administration number,and the red blood cell count did not change significantly,but was lower than that of the vehicle group(P＜0.05).Additionally,the absolute value of lymphocytes decreased while that of neutrophils and monocytes increased.The absolute value of neutrophils at 9 h increased 8.7 times after treatment,and was significantly higher than that of the vehicle group(P＜0.05).Apilimod 10-50 mg/kg increased neutrophils of mice in a dose-dependent manner at 9 h after a single intraperitoneal injection(R2=0.9556).Nine hours after injection of apilimod 40 mg/kg,the numbers of mononucleated cells(MNCs),immature hematopoietic cells(lin-)and lin-Sca-1-c-kit+ cells(LK)in the peripheral blood and spleen of the apilimod group were significantly larger than those of the vehicle group(P＜0.05).The number of lin-Sca-1+ c-kit+ cells(LSK)from spleens of apilimod-treated mice was significantly larger than that of vehicle treated mice(P＜0.05).There was no significant difference between apilimod and AMD3100 treated mice in LK or LSK from peripheral blood and spleens(P>0.05)or in the proportion and number of hematopoietic stem progenitor cells in femur bone marrow between the apilimod group and vehicle group(P>0.05).Apilimod administration changed the concentration of cytokines in serum.At 9 h post administration,the concentration of interferon-12p70(IL-12p70)decreased while those of interferon-10(IL-10)and tumor necrosis factor-α(TNF-α)increased 14.6 and 5.9 times,respectively.Conclusion apilimod has a significant regulatory effect on the number of hematopoietic cells in mice under steady-state conditions.Single intraperitoneal injection of apilimod can significantly affect the absolute value of mature blood cells in the peripheral blood of mice.Moreover,apilimod can increase the value of hematopoietic progenitor cells in peripheral blood and spleens,but has no effect on the value and cell cycle distribution of hematopoietic stem and progenitor cells in bone marrow.Furthermore,a single injection of apilimod resulted in a decrease in IL-12p70 levels,while increasing the concentrations of IL-10 and TNF-α in the serum.
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