Wednesday, 4 November 2009

Vitamin d-directed rheostatic regulation of monocyte antibacterial responses.
the active form of vitamin D, 1,25-dihydroxyvitamin D, Calcitriol, enhances innate immunity by inducing the cathelicidin antimicrobial peptide (hCAP).

In monocytes/macrophages, this occurs primarily in response to activation of TLR, that induce expression of the vitamin D receptor and localized synthesis of 1,25(OH)(2)D from precursor 25-hydroxyvitamin D(3) (25OHD) Calcidiol.

To clarify the relationship between vitamin D and innate immunity, we assessed changes in hCAP expression in vivo and ex vivo in human subjects attending a bone clinic.

Of these, 38% were vitamin D-insufficient (<75 nM 25OHD) and received supplementation with vitamin D (50,000 IU vitamin D(2) twice weekly for 5 wk). Only morons spend $185 on Drisdol Ergocaciferol when they can buy the same strength Vitamin D3 Cholecalciferol FOR $30 the form human use best, most efficiently and most reliably. I sometimes wonder if they use the synthetic form in the hope it is more likely to fail.

Baseline 25OHD status or vitamin D supplementation had no effect on circulating levels of hCAP.
Therefore, ex vivo changes in hCAP for each subject were assessed using peripheral blood monocytes cultured with 10% autologous serum.
Under these vitamin D "insufficient" conditions the TLR2/1 ligand 19 kDa lipopeptide or the TLR4 ligand LPS, monocytes showed increased expression of the vitamin D-activating enzyme CYP27b1 (5- and 5.5-fold, respectively, both p < 0.01) but decreased expression of hCAP mRNA (10-fold and 30-fold, both p < 0.001).
Following treatment with 19 kDa, expression of hCAP:
1) correlated with 25OHD levels in serum culture supplements (R = 0.649, p < 0.001);
2) was significantly enhanced by exogenous 25OHD (5 nM); and
3) was significantly enhanced with serum from vivo vitamin D-supplemented patients.

These data suggest that a key role of vitamin D in innate immunity is to maintain localized production of antibacterial hCAP following TLR activation of monocytes.