The Effects Of 1a,25-dihydroxyvitamin-D₃ On Interferon-gamma And Interleukin-10 Secretion In Peripheral Blood Mononuclear Cells Of Patients With Intrahepatic Cholestasis Of Pregnancy

Objective:To investigate the influence of 1a,25-dihydroxyvitamin-D₃ on interferon-gamma(IFN-γ)and interleukin-10 secretion(IL-10)production in peripheral blood mononuclear cells (PBMC)of patients with intrahepatic cholestasis of pregnancy(ICP).Method:PBMC of 20 patients with ICP(study group)and 20 normal pregnant women(control group)were isolated by human lymphocyte separation liquid.The PBMC of the ICP and control group resepectively incubated independently for 24h,48h and 72h with the different concertrations(0,10^-7,10^-8and 10^-9mol/L)of 1a,25-dihydroxyvitamin-D₃.Cytokines IFN-γ,and IL-10 secretions were measured in the supermatants by ELISA.Result:(1)Comparing with the levels of IFN-γin the control holes of normal group(6.87±0.96),(6.84±0.76),(6.71±0.84)pg/ml and the levels of IL-10(36.82±7.06),(35.30±9.23),(36.76±5.18)pg/ml after the PBMC incubated independently for 24h,48h and 72h,The levels of IFN-γof ICP group(16.42±1.38),(16.36±1.43),(16.21±1.15)pg/ml were more higher and the levels of IL-10(12.55±9.63),(13.47±8.35),(13.64±8.83)pg/ml were more lower(p＜0.05).(2)The PBMC of ICP group treated with 1a,25-(OH)₂D₃ of 10^-9mol/L,10^-8mol/L and 10^-7mol/L over 24h,48h and 72h,the levels of IFN-γwere(4.59±0.49),(4.43±0.67),(2.49±1.00)pg/ml; (2.64±0.52),(2.38±0.30),(1.45±0.59)pg/ml;(4.33±0.73),(4.34±0.67),(2.98±0.57)pg/ml,comparing with the levels of IFN-γin the control holes had a lower secretion of IFN-γ(p＜0.05).Under the same incubated phases,the levels of IFN-γwere much lower after treated with 1a,25-(OH)_D3 of 10^-8mol/L than treated with 1a,25-(OH)₂D₃ of 10^-7mol/L and 10^-9mol/L(p＜0.05),but the levels of IFN-γhad no differences between 10^-7mol/L and 10^-9mol/L(p＞0.05).Under the same density of 1a,25-(OH)₂D₃,the levels of IFN-γwere much lower after incubated for 72h than incubated for 24h and 48h(p＜0.05),but the levels of IFN-γhad no differences between incubated for 24h and 48h(p＞0.05).However,1a,25-(OH)₂D₃ in same concentration had no evident effect on the normal group(p＞0.05).(3)The PBMC of ICP group treated with 1a,25-(OH)₂D₃ of 10^-9mol/L,10^-8mol/L and 10^-7mol/L over 24h,48h and 72h,the levels of IL-10 were(58.80±5.15),(58.23±5.24),(66.02±4.38)pg/ml; (76.62±6.10),(78.10±6.60),(96.15±4.61)pg/ml;(58.23±7.53),(58.90±4.98),(68.07±5.40)pg/ml,comparing with the levels of IL-10 in the control holes had higher secretion of IL-10(p＜0.05).Under the same incubated phases,the levels of IL-10 were much higher after treated with 1a,25-(OH)₂D₃ of 10^-8mol/L than treated with 1a,25-(OH)₂D₃ of 10^-7 mol/L and 10⁽-9(mol/L(p＜0.05),but the levels of IL-10 had no differences between 10^-7mol/L and 10^-9mol/L(p＞0.05).Under the same density of la,25-(OH)₂D₃,the levels of IL-10 were much higher after incubated for 72h than incubated for 24h and 48h(p＜0.05),but the levels of IL-10 had no differences between incubated for 24h and 48h(p＞0.05).however,1a,25-(OH)₂D₃ in same concentration gave no evident effect to the normal group(p＞0.05).Conclution:1a,25-(OH)₂D₃ may probably inhibit the production of IFN-γ,but it could increase the levels of IL-10 in the condition of PBMC in vitro on ICP patients,and it probably worked depended on phase and concentration,especially be treated with 1a,25-(OH)₂D₃ of 10^-8mol/L incubating for 72h were the best.