title: Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation.
abstract: 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 non-infected 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 non-infected patients. In 12 non-infected PD patients, oral supplementation with a single dose of vitamin D2 (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.
authors.affiliation: Orthopedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America; Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America; Centre de Référence des Maladies Rénales Rares, Institut de Génomique Fonctionnelle à l'Ecole Normale Supérieure de Lyon et Université de Lyon, Lyon, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Bacchetta
authors.affiliation: Orthopedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Rene F
authors.initials: RF
authors.lastname: Chun
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gales
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Zaritsky
authors.affiliation: Unité d'épidémiologie des maladies émergentes, Institut Pasteur, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Leroy
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Wesseling-Perry
authors.affiliation: Department of Hematology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Boregaard
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Anjay
authors.initials: A
authors.lastname: Rastogi
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Isidro B
authors.initials: IB
authors.lastname: Salusky
authors.affiliation: Orthopedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
mesh_terms: D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D064451:Hepcidins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D010530:Peritoneal Dialysis; D010538:Peritonitis; D051436:Renal Insufficiency, Chronic / Q000628:therapy*; D014807:Vitamin D / Q000008:administration & dosage*; D055815:Young Adult; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D064451:Hepcidins; D014807:Vitamin D; D054804:Cathelicidins