Effects of different concentrations of voriconazole on THP-1-induced macrophage immune function

TENG Guojie; NIE Xiuhong

doi:10.3969/j.issn.1673-3827.2023.05.001

Abstract：Objective The aim of this study was to explore the effects of concentrations of voriconazole on the macrophages immune function induced by THP-1 cells.Methods Different concentrations of voriconazole were added to THP-1 induced macrophages,the final concentration of voriconazole was 0,0.25,0.5,1,2,4,8,16,32,64 μg/mL,and the inactivated Aspergillus fumigatus liquid(IAFL)was added,incubate for 6 hours.Tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)concentration in the culture supernatant were detected.Flow cytometry was used to de-tect the expression of Toll like receptor-2(TLR2),Toll like receptor-4(TLR4),and dendritic cell-associated C-type lectin-1(Dectin-1)on the macrophages membrane surface.Result When the concentration of voriconazole was between 4 and 64 μg/mL,the concentrations of TNF-α and IL-1β were significantly higher than those of the control group(containing only THP-1-derived macrophages and inactivated Aspergillus fumigatus liquid)(P<0.05).The concentrations of TNF-α and IL-1β peaked at voriconazole concentrations of 16 μg/mL and 8 μg/mL,respectively.There was no significant difference in IL-10 concentration among different voriconazole concentration groups(P all>0.05).When the concentration of voricon-azole was 1-64 μg/mL,the median fluorescence intensity of TLR2,TLR4,and Dectin-1 on the cell membrane surface was significantly higher than that of the IAFL control group(P<0.05).When voriconazole concentration was 4 μg/mL,4 μg/mL and 1 μg/mL,the average fluorescence intensity of TLR2,TLR4 and Dectin-1 on the cell membrane surface reached the peak.Conclusion In the presence of IAFL,the secretion of TNF-α and IL-1β from macrophages induced by THP-1 could be stimulated by voriconazole.The expression of TLR2,TLR4 and dectin-1 on the surface of macrophage membrane was en-hanced.However,the enhancement did not increase continuously with the increase of voriconazole dose.