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

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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 lowK m-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.

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Author notes

  1. Paul J. Marshall

    Present address: Miles Research Center, 400 Morgan Lane, 06516, West Haven, Connecticut

Authors and Affiliations

  1. Departments of Pharmacology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, Pennsylvania

    Don E. Griswold, Edward F. Webb, John Breton, Paul J. Marshall & Theodore J. Torphy

  2. Departments of Cell Biochemistry and Immunology, SmithKline Beecham Pharmaceuticals, P.O. Box 1539, 19406, King of Prussia, Pennsylvania

    John R. White

Authors
  1. Don E. Griswold
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  2. Edward F. Webb
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  3. John Breton
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  4. John R. White
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  5. Paul J. Marshall
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  6. Theodore J. Torphy
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Griswold, D.E., Webb, E.F., Breton, J. et al. Effect of selective phosphodiesterase type IV inhibitor, rolipram, on fluid and cellular phases of inflammatory response. Inflammation 17, 333–344 (1993). https://doi.org/10.1007/BF00918994

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