Plasma LL-37 correlates with vitamin D and is reduced in human immunodeficiency virus-1 infected individuals not receiving antiretroviral therapy

J Med Microbiol. 2014 Jul;63(Pt 7):997-1003. doi: 10.1099/jmm.0.070888-0. Epub 2014 May 12.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antimicrobial Cationic Peptides / metabolism*
  • Calcifediol / blood*
  • Calcifediol / metabolism
  • Calcitriol / blood*
  • Calcitriol / metabolism
  • Case-Control Studies
  • Cathelicidins
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Gene Expression Regulation, Viral
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV Infections / metabolism
  • HIV-1 / isolation & purification*
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio

Substances

  • Anti-HIV Agents
  • Antimicrobial Cationic Peptides
  • Calcitriol
  • Calcifediol
  • Cathelicidins