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

  • Lee Hyun Seung
    Biomedical Research Institute, Seoul National University Hospital
  • Park Heung-Woo
    Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center Department of Internal Medicine, Seoul National University Hospital Department of Internal Medicine, Seoul National University College of Medicine
  • Lee Suh-Young
    Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center Department of Internal Medicine, Seoul National University Hospital Department of Internal Medicine, Seoul National University College of Medicine Department of Molecular Microbiology and Immunology, Brown University

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<p>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.</p>

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