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Immunomodulatory gene expression analysis in LPS-stimulated human polymorphonuclear leukocytes treated with

Tsuneyuki Ubagai1, Yoshinori Sato1, Go Kamoshida1

  • 1Department of Microbiology & Immunology, Teikyo University School of Medicine Tokyo, 173-8605, Japan.

Molecular Immunology
|December 3, 2020
PubMed

Insights

Last-resort antibiotics like fosfomycin (FOM), levofloxacin (LVFX), and minocycline (MINO) can suppress the host

Area of Science:

  • Immunology
  • Microbiology
  • Pharmacology

Background:

  • Severe infections like sepsis and septic shock are often treated with conventional antibiotics that offer immunomodulatory benefits.
  • The rise of multidrug-resistant infections necessitates the use of last-resort antibiotics, such as quinolones, aminoglycosides, and polypeptides.
  • The impact of these non-conventional antibiotics on immunomodulatory gene expression in human polymorphonuclear leukocytes (PMNs) remains largely uncharacterized.

Purpose of the Study:

  • To investigate the effects of last-resort antibiotics on immunomodulatory gene expression in activated human PMNs.
  • To determine how antibiotics like fosfomycin (FOM), levofloxacin (LVFX), and minocycline (MINO) influence inflammatory cytokine and chemokine receptor expression.

Main Methods:

  • Human PMNs were stimulated with lipopolysaccharide and subsequently incubated with various antibiotics, including piperacillin, rifampicin, FOM, LVFX, MINO, colistin, tigecycline, and amikacin.
  • Real-time quantitative PCR (qPCR) was employed to measure the mRNA expression levels of pattern recognition receptors (TLR2, TLR4, CD14), inflammatory cytokines (TNFα, IL6), and chemokine receptors (IL8Rs, ITGAM).

Main Results:

  • Several tested antibiotics demonstrated an ability to alter the expression of investigated cytokines.
  • Notably, FOM, LVFX, and MINO significantly downregulated the expression of IL6, a cytokine involved in both pro- and anti-inflammatory responses.
  • Treatment with FOM and LVFX led to reduced IL-6 production, correlating with observed gene expression changes, suggesting transcriptional and translational cooperation.

Conclusions:

  • The administration of certain last-resort antibiotics, including FOM, LVFX, and MINO, may suppress the host's anti-inflammatory response.
  • These findings highlight the complex interplay between non-conventional antibiotics and the host immune system, particularly in the context of multidrug-resistant infections.
Keywords:
AntibioticsLeukocyteLipopolysaccharideMultidrug resistancePolymorphonuclearToll-like receptors

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