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

Inflammation. 1993 Jun;17(3):333-44. doi: 10.1007/BF00918994.

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 microM). 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 low Km-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.

Publication types

  • Comparative Study

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arachidonic Acid / toxicity
  • Calcimycin / pharmacology
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Ear, External
  • Eicosanoids / metabolism
  • Histamine Release / drug effects
  • Humans
  • Imidazoles / pharmacology
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Leukotriene B4 / biosynthesis
  • Male
  • Mast Cells / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / drug effects
  • Nadolol / pharmacology
  • Naproxen / pharmacology
  • Neutrophils / drug effects*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases* / physiology
  • Purinones / pharmacology
  • Pyrazoles / pharmacology
  • Pyrrolidinones / pharmacology*
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Rolipram
  • SRS-A / metabolism
  • Thiazoles / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Eicosanoids
  • Imidazoles
  • Phosphodiesterase Inhibitors
  • Purinones
  • Pyrazoles
  • Pyrrolidinones
  • Receptors, Adrenergic, beta
  • SRS-A
  • Thiazoles
  • Colforsin
  • Leukotriene B4
  • Arachidonic Acid
  • Calcimycin
  • Nadolol
  • Naproxen
  • 6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • zaprinast
  • phenidone
  • Rolipram