Levels of vitamin D-associated cytokines distinguish between active and latent tuberculosis following a tuberculosis outbreak

BMC Infect Dis. 2019 Feb 13;19(1):151. doi: 10.1186/s12879-019-3798-5.

Abstract

Background: Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI).

Methods: In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma 25-hydroxyvitamin D (25[OH]D), IL-15, IL-32, and IL-1β levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay.

Results: Plasma 25(OH)D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (25(OH)D: 16.64 ng/mL vs. 21.6 ng/mL, P = 0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P = 0.013). Plasma 25(OH)D levels correlated with the plasma levels of IL-15 and IL-1β in TB-infected patients. In addition, the plasma 25(OH)D levels correlated positively with the level of unstimulated IL-15 (IL-15nil) and negatively with that of TB antigen-stimulated IL-32 (IL-32TB) in QFT-GIT supernatants. Although the IL-15nil and IL-15TB levels were higher in LTBI subjects than patients with active TB, the IL-32nil and IL-32TB levels were higher in the latter patients. A combination of the IL-15nil and IL-32TB levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964.

Conclusions: Our preliminary data showed that the levels of the vitamin D-related cytokines IL-15 and IL-32 differed between active TB patients and LTBI subjects. This result might be used as a basic data for developing biomarkers distinguishing between active TB and LTBI.

Keywords: Cytokine; Tuberculosis; Vitamin D.

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Cytokines / blood*
  • Diagnostic Tests, Routine
  • Disease Outbreaks
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-15 / blood
  • Interleukins / blood
  • Latent Tuberculosis / blood*
  • Latent Tuberculosis / diagnosis
  • Latent Tuberculosis / epidemiology
  • Male
  • Mycobacterium tuberculosis / immunology
  • Republic of Korea / epidemiology
  • Tuberculosis / blood*
  • Tuberculosis / diagnosis
  • Tuberculosis / epidemiology
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood*

Substances

  • Biomarkers
  • Cytokines
  • IL15 protein, human
  • IL32 protein, human
  • Interleukin-15
  • Interleukins
  • Vitamin D
  • 25-hydroxyvitamin D