title: Single nucleotide polymorphic macrophage cytokine regulation by Mycobacterium tuberculosis and drug treatment.
abstract: OBJECTIVE
  To investigate the survival of Mycobacterium tuberculosis in primary macrophages with SNPs affecting cytokine secretion under treatment with drugs in solution or microparticles.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pharmaceutics Division, CSIR Central Drug Research Institute, Sector 10, Janakipuram Extension, Lucknow 226031, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Singh
authors.forename: Awadh Bihari
authors.initials: AB
authors.lastname: Yadav
authors.forename: Rajiv
authors.initials: R
authors.lastname: Garg
authors.forename: Amit
authors.initials: A
authors.lastname: Misra
mesh_terms: D000328:Adult; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics*; D048069:Tumor Necrosis Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; C508598:IL4 protein, human; D004364:Pharmaceutical Preparations; D048069:Tumor Necrosis Factors; D016753:Interleukin-10; D015847:Interleukin-4