Antibacterial Responses by Peritoneal Macrophages Are Enhanced Following Vitamin D Supplementation

作者:Bacchetta Justine; Chun Rene F; Gales Barbara; Zaritsky Joshua J; Leroy Sandrine; Wesseling Perry Katherine; Boregaard Niels; Rastogi Anjay; Salusky Isidro B; Hewison Martin*
来源:PLos One, 2014, 9(12): e116530.
DOI:10.1371/journal.pone.0116530

摘要

Patients with chronic kidney disease (CKD), who usually display low serum 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are at high risk of infection, notably those undergoing peritoneal dialysis (PD). We hypothesized that peritoneal macrophages from PD patients are an important target for vitamin D-induced antibacterial activity. Dialysate effluent fluid was obtained from 27 noninfected PD patients. Flow cytometry indicated that PD cells were mainly monocytic (37.9 +/- 17.7% cells CD14(+)/CD45(+)). Ex vivo analyses showed that PD cells treated with 25D (100 nM, 6 hrs) or 1,25D (5 nM, 6 hrs) induced mRNA for antibacterial cathelicidin (CAMP) but conversely suppressed mRNA for hepcidin (HAMP). PD cells from patients with peritonitis (n=3) showed higher baseline expression of CAMP (18-fold +/- 9, p<0.05) and HAMP (64-fold +/- 7) relative to cells from noninfected patients. In 12 non-infected PD patients, oral supplementation with a single dose of vitamin D-2 (100,000 IU) increased serum levels of 25D from 18 +/- 8 to 41 +/- 15 ng/ml (p=0.002). This had no significant effect on PD cell CD14/CD45 expression, but mRNA for HAMP was suppressed significantly (0.5-fold, p=0.04). Adjustment for PD cell CD14/CD45 expression using a mixed linear statistical model also revealed increased expression of CAMP (mRNA in PD cells and protein in effluent) in vitamin D-supplemented patients. These data show for the first time that vitamin D supplementation in vitro and in vivo promotes innate immune responses that may enhance macrophage antibacterial responses in patients undergoing PD. This highlights a potentially important function for vitamin D in preventing infection-related complications in CKD.

  • 出版日期2014-12-30