Research Article
Galina V. Volodina, Tigran
Abstract
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