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Inflammation

, Volume 17, Issue 3, pp 333–344 | Cite as

Effect of selective phosphodiesterase type IV inhibitor, rolipram, on fluid and cellular phases of inflammatory response

  • Don E. Griswold
  • Edward F. Webb
  • John Breton
  • John R. White
  • Paul J. Marshall
  • Theodore J. Torphy
Original Articles

Abstract

The antiinflammatory activity of rolipram, a selective inhibitor of the cyclic AMP-specific phosphodiesterase (PDE IV), was studied. Rolipram did not inhibit 5-lipoxygenase activity but did inhibit human monocyte production of leukotriene B4 (LTB4, IC50 3.5 μM). Likewise, murine mast cell release of leukotriene C4 and histamine was inhibited. In vivo, rolipram inhibited arachidonic acid-induced inflammation in the mouse, while the lowKm-cyclic-GMP PDE inhibitor, zaprinast, did not inhibit. Rolipram had a modest effect on LTB4 production in the mouse, but markedly reduced LTB4-induced PMN infiltration. Beta-adrenergic receptor activation of adenylate cyclase was important for rolipram antiinflammatory activity since beta blockade abrogated arachidonic acid-induced inflammation. Thus, the antiinflammatory profile of rolipram is novel and may result from inhibition of PMN function and perhaps vasoactive amine release and leukotriene biosynthesis. These actions may be dependent upon endogenous beta-adrenergic activity and are likely mediated through inhibition of PDE IV.

Keywords

LTB4 Rolipram Zaprinast Vasoactive Amine LTB4 Production 
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.

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Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • Don E. Griswold
    • 1
  • Edward F. Webb
    • 1
  • John Breton
    • 1
  • John R. White
    • 2
  • Paul J. Marshall
    • 1
  • Theodore J. Torphy
    • 1
  1. 1.Departments of PharmacologySmithKline Beecham PharmaceuticalsKing of Prussia
  2. 2.Departments of Cell Biochemistry and ImmunologySmithKline Beecham PharmaceuticalsKing of Prussia

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