Rapamycin Restores Different Patterns of Cytokine Expression to Dexamethasone Treatment on CD14++CD16+ Monocytes from Steroid-Resistant Asthma Patients

Biol Pharm Bull. 2023;46(4):542-551. doi: 10.1248/bpb.b22-00480.

Abstract

Objective: We aimed to investigate the differences in interleukin (IL)-10, IL-1β, IL-6, and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated CD14++CD16+ monocytes obtained from asthmatics after dexamethasone or dexamethasone plus rapamycin treatments between clinical steroid responders (R) and non-responders (NR).

Methods: Cytokine expressions in LPS-stimulated CD14++CD16+ p-mammalian target of rapamycin (mTOR) monocytes from R and NR were determined using flow cytometry.

Results: IL-10high CD14++CD16+ p-mTOR population following LPS stimulation increased in the R group although decreased in the NR group with dexamethasone treatment. IL-1βhigh population decreased in the R group although increased in the NR group. Rapamycin treatment after LPS and dexamethasone resulted in a significant increase in the IL-10high population and a significant decrease in the IL-1βhigh population in the NR group.

Conclusion: Dexamethasone treatment resulted in different patterns of change in cytokine expressions in LPS-stimulated CD14++CD16+ p-mTOR monocytes between the R and NR. mTOR inhibition can restore steroid responsiveness involving IL-10 and IL-1β in CD14++CD16+ p-mTOR monocytes.

Keywords: asthma; lipopolysaccharide; monocyte; steroid; target of rapamycin (TOR) serine-threonine kinase.

MeSH terms

  • Asthma* / drug therapy
  • Asthma* / metabolism
  • Cytokines* / metabolism
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Humans
  • Interleukin-10 / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / pharmacology
  • Monocytes
  • Receptors, IgG / metabolism
  • Steroids
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Interleukin-10
  • Lipopolysaccharides
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Dexamethasone
  • Steroids