Advertisement

Agents and Actions

, Volume 39, Supplement 1, pp C70–C72 | Cite as

The effects of anti-inflammatory and antiallergic drugs on the release of IL-1β and TNF-α in the human whole blood assay

  • D. A. Hartman
  • S. J. Ochalski
  • R. P. Carlson
Regulation of Cytokinses

Abstract

Heparinized human whole blood was evaluated as a model to study the effects of various classes of anti-inflammatory drugs on IL-1β and TNF-α release from leukocytes. Human whole blood was stimulated with zymosan (1.5 mg/ml) or LPS (5 μg/ml) to induce significant cytokine release. As previously reported, the 5-lipoxygenase/cyclooxygenase (5-LO/CO) inhibitor, SKF86002 (30 μM), significantly inhibited both IL-1β and TNF-α release using either stimulus. In contrast, the cyclooxygenase (CO) inhibitors (naproxen and ibuprofen) and the lipoxygenase (5-LO) inhibitors (zileuton, L-663536 and BWA4C) did not effect IL-1β or TNF-α release/biosynthesis. Isoproterenol (β-agonist), rolipram (a PDE-IV inhibitor), and IBMX (a nonselective PDE inhibitor), significantly inhibited TNF-α but not IL-1β in the LPS model while having no effect in the zymosan model. This human whole blood assay is a unique and rapid method which can be used to identify novel inhibitors of IL-1β and TNF-α release/biosynthesis.

Keywords

Ibuprofen Naproxen Isoproterenol Rapid Method Cytokine Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. [1]
    L. E. DeForge, J. S. Kenney, M. L. Jones, J. S. Warren and D. G. Remick,Biphasic production of IL-8 in lipopolysaccharide (LPS)-stimulated human whole blood. J. Immunol.148, 2133–2141 (1992).PubMedGoogle Scholar
  2. [2]
    L. E. DeForge and D. G. Remick,Kinetics of TNF, IL-6 and IL-8 gene expression in LPS-stimulated human whole blood. Biochem. Biophys. Res. Commun.174, 18–24 (1991).CrossRefPubMedGoogle Scholar
  3. [3]
    Mikko Hurme,Modulation of interleukin-1β production by cyclic AMP in human monocytes. FEBS Lett.263, 35–37 (1990).CrossRefPubMedGoogle Scholar
  4. [4]
    S. Endres, H. J. Fulle, B. Sinha, D. Stoll, C. A. Dinarello, R. Gerzer and P. C. Weber,Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-α and interleukin-1β by human mononuclear cells. Immunology72, 56–60 (1991).PubMedGoogle Scholar
  5. [5]
    J. C. Lee, B. Votta, B. J. Dalton, D. E. Griswold, P. E. Bender and N. Hanna,Inhibition of human monocyte IL-1 production by SK&F 86002. Int. J. ImmunotherapyVI, 1–12 (1990).Google Scholar
  6. [6]
    R. M. Strieter, D. G. Remick, P. A. Ward, R. N. Spemgler, J. P. Lynch III, J. Larrick and S. L. Kunkel,Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem. Biophys. Res. Commun.155, 1230–1236 (1988).CrossRefPubMedGoogle Scholar
  7. [7]
    C. S. Tannenbaum and T. A. Hamilton,Lipopolysaccharide-induced gene expression in murine peritoneal macrophages is selectively suppressed by agents that elevate intracellular cAMP. J. Immunol.142, 1274 (1989).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • D. A. Hartman
    • 1
  • S. J. Ochalski
    • 1
  • R. P. Carlson
    • 1
  1. 1.Wyeth-Ayerst Research, CN-8000PrincetonUSA

Personalised recommendations