title: Plasma LL-37 correlates with vitamin D and is reduced in human immunodeficiency virus-1 infected individuals not receiving antiretroviral therapy.
abstract: Low levels of the vitamin D-regulated antimicrobial peptide cathelicidin (LL-37) may negatively impact the immune status of human immunodeficiency virus-1 (HIV-1) infected individuals (HIV+). We compared plasma LL-37 levels in healthy controls (HIV-) and HIV+ individuals on or off antiretroviral therapies (ARTs) (ART+ and ART-, respectively), and evaluated the relationship between vitamin D and LL-37 levels. In this cross-sectional study, levels of LL-37, 25-hydroxycholecalciferol [25(OH)D3] and 1,25-dihydroxycholecalciferol [1,25(OH)2D3] were measured from an initial cohort of 18 healthy controls and 10 HIV+/ART- individuals. Because this cohort lacked HIV+/ART+ subjects, LL-37 was also quantified from a second cohort of 10 HIV+/ART- and 13 HIV+/ART+ individuals. LL-37 levels were significantly lower in the HIV+/ART- group compared to the healthy controls (P = 0.01). A direct relationship was observed between LL-37 and both 25(OH)D3 and 1,25(OH)2D3. The level of 25(OH)D3 was predictive of higher LL-37 (P = 0.04) and for any given level of 25(OH)D3, HIV+/ART- subjects averaged 20 % lower LL-37 compared to the healthy controls (P = 0.045). For any given level of 1,25(OH)2D3, HIV+/ART- subjects averaged 25% lower LL-37 compared to the healthy controls (P = 0.018), although 1,25(OH)2D3 was not predictive of higher LL-37 (P = 0.28). Finally, LL-37 levels were significantly lower in the HIV+/ART- group compared to the HIV+/ART+ group from the second cohort (P = 0.045). Untreated HIV infection may contribute to lower LL-37 levels, independent of vitamin D levels. ART treatment may potentially mitigate this decrease in LL-37 levels.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Honda
authors.affiliation: Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Connick
authors.affiliation: Colorado School of Public Health, Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: MaWhinney
authors.affiliation: National Jewish Health and Denver Veterans Affairs Medical Center, Denver, CO 80220, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Chan
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Flores
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D002112:Calcifediol / Q000097:blood* / Q000378:metabolism; D002117:Calcitriol / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D054804:Cathelicidins
chemical_list: D019380:Anti-HIV Agents; D023181:Antimicrobial Cationic Peptides; D002117:Calcitriol; D002112:Calcifediol; D054804:Cathelicidins