Effect of 1,25-dihydroxy-vitamin D3 in experimental sepsis

Abstract

In addition to the regulation of calcium homeostasis, vitamin D affects the cellular immune system, targets the TNF-alpha pathway and increases vasoconstrictor response to angiotensin II. We therefore examined the effect of 1,25-dihydroxy-vitamin D(3) on coagulation and organ failure in experimental sepsis in the rat. Three series of placebo-controlled studies were conducted. All rats were pre-treated with daily SC injections of 1,25-dihydroxy-vitamin D(3) 100 ng/kg or placebo vehicle for 3 days. In study 1, sepsis was accomplished by abdominal surgery comprising a coecal ligation and puncture with a 1,2 mm needle, or sham surgery. In study 2, the rats had a single IP injection of lipopolysaccharide from E. Coli 0111:B4 (LPS) 8 mg/kg, or placebo. In study 3, an hour-long IV infusion of LPS 7 mg/kg, or placebo was given. All three models of sepsis showed significant effects on coagulation and liver function with reduced thrombocyte count and prothrombin time together with elevated ALT and bilirubin (p<0.05) as compared to controls. In study 1, the vitamin D treated rats maintained normal platelet count, whereas the vehicle treated rats showed a significant reduction (p<0.05). This effect of vitamin D on platelets was not found in the LPS-treated groups. We found no significant differences between vitamin D and placebo-treated rats with regards to liver function. The present data suggest a positive modulating effect of 1,25-dihydroxy-vitamin D(3) supplementation on sepsis-induced coagulation disturbances in the coecal ligation and puncture model. No such effect was found in LPS-induced sepsis.