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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Møller
Søren
S
Department of Anaesthesiology, Frederiksberg Hospital, University of Copenhagen, Denmark.
Laigaard
Finn
F
Olgaard
Klaus
K
Hemmingsen
Claus
C
D000818:Animals; D002117:Calcitriol / Q000627:therapeutic use*; D002432:Cecum / Q000601:surgery; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology; D008026:Ligation; D008070:Lipopolysaccharides; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications / Q000188:drug therapy*; D014815:Vitamins / Q000627:therapeutic use*
D008070:Lipopolysaccharides; D014815:Vitamins; D002117:Calcitriol