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

Abstract

Aims: To investigate survival of Mycobacterium tuberculosis in primary macrophages with single nucleotide polymorphisms (SNPs) affecting cytokine secretion, under treatment with drugs in solution or microparticles. Materials & Methods: Volunteers were typed for tumor necrosis factor (TNF) (-308 G/A), interleukin (IL)-10 (-1082 A/G) and IL-4 (-590 C/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 CC and TT (P<0.1). Bacteria proliferated more in MDMs from volunteers with higher IL-4 (P<0.05). Microparticles showed higher efficacy (P<0.05) than drugs. Conclusions: IL-4 and IL-10 SNPs affect the ability of macrophages to counter infection with M tuberculosis. Microparticles elicit favourable macrophage cytokines regardless of SNPs.