Single Nucleotide Polymorphic Macrophage Cytokine Regulation by Mycobacterium tuberculosis and Drug Treatment

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.

Original submitted 5 August 2013; Revision submitted 27 November 2013

KEYWORDS::

• inhalable microparticles
• interleukin 10
• interleukin 4
• isoniazid
• rifabutin
• SNPs
• tumor necrosis factor

Acknowledgements

Help from AL Vishwakarma, Sophisticated Analytical Instruments Facility, CSIR-CDRI in running the flow cytometer is gratefully acknowledged.

Financial & competing interests disclosure

This is CDRI communication number 8573, supported by the Council of Scientific and Industrial Research, India (CSIR); through Senior Research Fellowships to AK Singh and AB Yadav and research funds through CSIR grants BSC0112 and ESC0101. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This is CDRI communication number 8573, supported by the Council of Scientific and Industrial Research, India (CSIR); through Senior Research Fellowships to AK Singh and AB Yadav and research funds through CSIR grants BSC0112 and ESC0101. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.