Inflammation Research

, Volume 54, Issue 1, pp 37–41

Rapid non-genomic inhibitory effects of glucocorticoids on human neutrophil degranulation

  • L. Liu
  • Y. X. Wang
  • J. Zhou
  • F. Long
  • H. W. Sun
  • Y. Liu
  • Y. Z. Chen
  • C. L. Jiang
Original Research Paper

DOI: 10.1007/s00011-004-1320-y

Cite this article as:
Liu, L., Wang, Y.X., Zhou, J. et al. Inflamm. res. (2005) 54: 37. doi:10.1007/s00011-004-1320-y

Abstract.

Background: Glucocorticoids acting as anti-inflammatory or immunosuppressive drugs have been shown to exert most of their effects genomically. Recent findings suggest that non-genomic activity might be relatively more important in mediating the therapeutic effects of high-dose pulsed glucocorticoid. However, few non-genomic anti-inflammatory effects were reported, much less non-genomic mechanisms.

Objective: This study was performed to investigate the nongenomic effects of glucocorticoids on human neutrophil degranulation.

Methods: Purified human neutrophils were pretreated with 6 α-methylprednisolone or hydrocortisone for 5 min, and then primed with N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10−6 M) or phorbol myristate acetate (PMA) (50 ng/ml) in the presence of cytochalasin B. The release of two markers of neutrophil granules, lactoferrin and myeloperoxidase, was measured by ELISA and enzymology methods respectively.

Results: Both 6 α-methylprednisolone (10−5–10−4 M) and hydrocortisone (10−4 M) showed significant inhibitory effects on neutrophil degranulation within 5 min after fMLP administration. For PMA stimulated degranulation, 6 α-methylprednisolone (10−4 M) showed significant inhibitory effects (p < 0.01), while hydrocortisone (10−4 M) only showed an inhibitory tendency (P > 0.05). Neither RU486 (10−5 M) nor cycloheximide (10−4 M) could alter the inhibitory effects of glucocorticoids.

Conclusion: Our results demonstrate that megadoses of glucocorticoids exert rapid inhibitory effects on human neutrophil degranulation at the cellular level via a new mechanism that is independent of corticosteroid type II receptor occupation or protein synthesis. We infer that these effects may be very important when glucocorticoids act as anti-inflammatory drugs during pulse therapy.

Key words.

GlucocorticoidsNon-genomic actionNeutrophilDegranulationAnti-inflammation

Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • L. Liu
    • 1
  • Y. X. Wang
    • 1
  • J. Zhou
    • 1
  • F. Long
    • 1
  • H. W. Sun
    • 1
  • Y. Liu
    • 1
  • Y. Z. Chen
    • 2
  • C. L. Jiang
    • 1
  1. 1.Department of Nautical MedicineSecond Military Medical UniversityShanghaiP.R. of China
  2. 2.Department of NeurobiologySecond Military Medical UniversityShanghaiP.R. of China