Журнал клинической и клеточной иммунологии
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The Effect of Antibiotic-Resistant and Sensitive Escherichia coli on theProduction of Pro-Inflammatory Cytokine Response by Human PeripheralBlood Mononuclear Cells

Galina V. Volodina, Tigran K. Davtyan*, Murat E. Kulmanov, Ardak B. Dzhumagazieva, Sholpan K. Tursunova, Assima O. Abekova1, Indira E. Bishimova, Zhansaya S. Abramova, Roza T. Kenzhebekova, Sabina G. Murzageldinova, Ilya S. Korotetskiy and Alexander I. Ilin

Purpose: A comparative study of the effect of Escherichia coli, differing in gentamicin sensitivity, on the production of human pro-inflammatory cytokines IL-1β, IL-6, TNF-α by human peripheral blood mononuclear cells (PBMC) was carried out to determine the threshold for cytokine response induction. Methods: The multiple drug resistant E. coli strain ATCC-VAA-196 and its derivatives: a gentamicin-resistant E. coli strain R, obtained by prolonged cultivation of bacteria in the presence of antibiotics, and a gentamicin-sensitive strain of E. coli Rev, obtained by prolonged cultivation in the presence of new drug FS-1, were selected for this study. To determine the cytokine minimum inducing concentration (cMIC) for live (carrying DAMPs) and formalin-fixed (exposing canonical PAMPs) E. coli strains, PBMC were co-cultured with different concentrations of bacteria, and the level of cytokine production was measured using an enzyme immunoassay. Results: The PAMP-and DAMP-mediated differences in the threshold for induction of proinflammatory cytokines IL-1β, IL-6, TNF-α production by PBMC treated with bacteria that differ in the sensitivity phenotype were found to be corresponding. cMIC for the initial resistant E. coli strain BAA-196 and the gentamicin-resistant E. coli R strain (103 CFU/ml) was ten times lower than cMIC for the gentamicin-susceptible strain E. coli Rev (104 CFU/ml). Conclusion: The ability of the gentamicin-sensitive strain to exceedingly increase the threshold for induction of pro-inflammatory cytokine response of PBMC in comparison with the resistant strains appears to be an immunological evidence for reversion of antibiotic resistance towards restoring sensitivity to gentamicin