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1,25-dihydroxyvitamin D_3 regulates LPS-induced cytokine production and reduces mortality in rats

         

摘要

AIM: To study the immunoregulatory effect of 1,25-dihydroxyvitamin-D3 Von dominant Th1 response in rats. METHODS: Sixty adult Lewis rats were randomized into three groups. Rats in group 1 (n=25) were treated with 1,25-(OH)2D3 fi rst and then challenged with LPS,rats in group 2 (n=25) were treated with vehicle fi rst and then challenged with LPS. Ten animals in groups 1 and 2 were preserved for mortality observation. The remaining animals were injected (i.p) with endotoxin,24 h after the last administration of 1,25-(OH)2D3 and vehicle. Rats in group 3 (n =10) were treated with 1,25-(OH)2D3 only. Serum IL-12,IFN-γ,IL-2 and IL-4 levels were measured and target gene of 1,25-(OH)2D3 on Th cells was studied after 6 h. Gene abundance was verifi ed by real-time quantitative PCR. RESULTS: No death occurred in rats pretreated with 1,25-(OH)2D3 after LPS injection. Death occurred 9 h after LPS injection in rats pretreated with the vehicle,and the number of deaths was 5 within 24 h,with a mortality rate of 50%. There was no change in the number of deaths within 96 h. Six hours after endotoxin stimulation,serum IL-12 and IFN-γ levels decreased signifi cantly in rats pretreated with 1,25-(OH)2D3 as compared with those in rats pretreated with the vehicle. The serum content of these two cytokines was very low in rats not challenged by endotoxin,and there was a signifi cant difference as compared with the previous two groups. CONCLUSION: 1,25-(OH)2D3 attenuates injuryinduced by the lethal dose of LPS,regulates Th1 and Th2 cells at the transcription level,and dominantly responds to cytokine production in rats.

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