Aim
To study the immunoregulatory effect of 1,25-dihydroxyvitamin-D(3) Von dominant Th1 response in rats.
Conclusion
1,25-(OH)(2)D(3) attenuates injury induced by the lethal dose of LPS, regulates Th1 and Th2 cells at the transcription level, and dominantly responds to cytokine production in rats.
Methods
Sixty adult Lewis rats were randomized into three groups. Rats in group 1 (n=25) were treated with 1,25-(OH)(2)D(3) first and then challenged with LPS, rats in group 2 (n=25) were treated with vehicle first 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)(2)D(3) and vehicle. Rats in group 3 (n=10) were treated with 1,25-(OH)(2)D(3) only. Serum IL-12, IFN-gamma, IL-2 and IL-4 levels were measured and target gene of 1,25-(OH)(2)D(3) on Th cells was studied after 6 h. Gene abundance was verified by real-time quantitative PCR.
Results
No death occurred in rats pretreated with 1,25-(OH)(2)D(3) 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-gamma levels decreased significantly in rats pretreated with 1,25-(OH)(2)D(3) 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 significant difference as compared with the previous two groups.