title: Vitamin D supplementation and antibacterial immune responses in adolescents and young adults with HIV/AIDS.
abstract: Human monocytes activated by toll-like receptor 2/1 ligand (TLR2/1L) show enhanced expression of the vitamin D receptor (VDR) and the vitamin D-activating enzyme 1α-hydroxylase (CYP27B1). The resulting intracrine conversion of precursor 25-hydroxyvitamin D3 (25OHD) to active 1,25-dihydroxyvitamin D (1,25(OH)2D) can stimulate expression of antibacterial cathelicidin (CAMP). To determine whether this response is functional in HIV-infected subjects (HIV+ ), serum from HIV+ subjects pre- and post-vitamin D supplementation was utilized in monocyte cultures with or without TLR2/1L. Expression of CYP27B1 and VDR was enhanced following treatment with TLR2/1L, although this effect was lower in HIV+ vs HIV- serum (p<0.05). CAMP was also lower in TLR2/1L-treated monocytes cultured in HIV+ serum (p<0.01). In a dose study, supplementation of HIV+ subjects with 4000IU or 7000IU vitamin D/day increased serum 25OHD from 17.3±8.0 and 20.6±6.2ng/ml (43nM and 51nM) at baseline to 41.1±12.0 and 51.9±23.1ng/ml (103nM and 130nM) after 12 weeks (both p<0.001). Greater percent change from baseline 25OHD was significantly associated with enhanced TLR2/1L-induced monocyte CAMP adjusted for baseline expression (p=0.009). In a randomized placebo-controlled trial, 7000IU vitamin D/day increased serum 25OHD from 18.0±8.6 to 32.7±13.8ng/ml (45nM and 82nM) after 12 weeks. Expression of CAMP increased significantly from baseline after 52 weeks of vitamin D-supplementation. At this time point, TLR2/1L-induced CAMP was positively associated with percent change from baseline in 25OHD (p=0.029 overall and 0.002 within vitamin D-supplemented only). These data indicate that vitamin D supplementation in HIV-infected subjects can promote improved antibacterial immunity, but also suggest that longer periods of supplementation are required to achieve this.
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopedic Hospital, University of California, Los Angeles, CA 90095, USA.
authors.forename: Rene F
authors.initials: RF
authors.lastname: Chun
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopedic Hospital, University of California, Los Angeles, CA 90095, USA.
authors.forename: Nancy Q
authors.initials: NQ
authors.lastname: Liu
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopedic Hospital, University of California, Los Angeles, CA 90095, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lee
authors.affiliation: Gastroenterology, Hepatology and Nutrition, USA.
authors.forename: Joan I
authors.initials: JI
authors.lastname: Schall
authors.affiliation: Division of Nephrology, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Denburg
authors.affiliation: General Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Rutstein
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopedic Hospital, University of California, Los Angeles, CA 90095, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Adams
authors.affiliation: Gastroenterology, Hepatology and Nutrition, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104.
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.affiliation: Gastroenterology, Hepatology and Nutrition, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Stallings
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopedic Hospital, University of California, Los Angeles, CA 90095, USA. Electronic address: mhewison@mednet.ucla.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
mesh_terms: D000293:Adolescent; D000328:Adult; D019587:Dietary Supplements; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D014807:Vitamin D / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D014815:Vitamins; D014807:Vitamin D
keywords: Antibacterial; Cathelicidin; HIV; Monocytes; Vitamin D-supplementation
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