Beneficial effect of the active form of vitamin D-3 against LPS-induced DIC but not against tissue-factor-induced DIC in rat models

1 alpha ,25-dihydroxyvitamin D-3 (active form of vitamin D-3: vitamin D-3) has been reported to induce: the upregulation of thrombomodulin and downreg ulation of tissue factor (TF) on monocytes. The possibility exists that vit amin D-3 prevents the development of disseminated intravascular coagulation (DIC). In particular, monocyte TF production plays an important role in th e pathophysiology of DIC in septic patients. We have attempted to determine whether vitamin DI is effective against DIC in a rat model induced by lipo polysaccharides (LPS) (30 mg/kg, 4 h) or TF (3.75 U/kg, 4 h) using selectiv e hemostatic parameters, markers of organ dysfunction and pathological find ings (assessment of glomelular fibrin deposition). Vitamin D-3 was administ ered orally each day at a dose of 2.0 mg/kg/day for 3 days, or low molecula r weight heparin (LMWH 200 u/kg; I.V.) was given 10 min before the injectio n of TF or LPS in each treatment group. Vitamin D-3 was effective against D IC in the rat model induced by LPS only, whereas LMWH was effective against DIC in both rat models induced by either TF or LPS. The anti-DIG effect of vitamin D-3 was equal to (or more potent than) that of LMWH. The results s uggested that vitamin D-3 was useful for the treatment of LPS-induced DIG, and that the assessment of a drug's efficacy should be done carefully given the markedly different results obtained according to the agents used to in duce DIG.