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, 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


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.


Ibuprofen Naproxen Isoproterenol Rapid Method Cytokine Release 
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  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

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