1,25-dihydroxyvitamin D(3) regulates LPS-induced cytokine production and reduces mortality in rats

To study the immunoregulatory effect of 1,25-dihydroxyvitamin-D(3) Von dominant Th1 response in rats.

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.

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.

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.