Single nucleotide polymorphic macrophage cytokine regulation by Mycobacterium tuberculosis and drug treatment

Pharmacogenomics. 2014 Mar;15(4):497-508. doi: 10.2217/pgs.13.240.

Abstract

Aim: To investigate the survival of Mycobacterium tuberculosis in primary macrophages with SNPs affecting cytokine secretion under treatment with drugs in solution or microparticles.

Materials & methods: Volunteers were typed for TNF (-308G/A), IL-10 (-1082A/G) and IL-4 (-590C/T). Monocyte-derived macrophages (MDMs) were infected in vitro. Cytokine secretion and survival of intracellular bacilli were estimated.

Results: IL-10 AG associated with high secretion in uninfected and infected MDMs (p < 0.05) and was reduced more effectively by microparticles than drugs, irrespective of genotype (p < 0.05). Differences were observed between IL-4 secretion by MDMs of CC and TT genotypes (p = 0.1). Bacteria proliferated more in MDMs from volunteers with higher IL-4 levels (p = 0.05). Microparticles showed higher efficacy (p = 0.05) than drugs.

Conclusion: IL-4 and IL-10 SNPs affect the ability of macrophages to counter infection with M. tuberculosis. Microparticles elicit favorable macrophage cytokines regardless of SNPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines / genetics*
  • Female
  • Genotype
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-4 / genetics
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Male
  • Mycobacterium tuberculosis / drug effects*
  • Pharmaceutical Preparations / administration & dosage*
  • Polymorphism, Single Nucleotide / genetics*
  • Tuberculosis / drug therapy*
  • Tuberculosis / genetics*
  • Tumor Necrosis Factors / genetics
  • Young Adult

Substances

  • Cytokines
  • IL4 protein, human
  • Pharmaceutical Preparations
  • Tumor Necrosis Factors
  • Interleukin-10
  • Interleukin-4