Phosphodiesterase inhibitors suppress proliferation of peripheral blood mononuclear cells and interleukin-4 and -5 secretion by human T-helper type 2 cells

Immunopharmacology. 1996 Mar;31(2-3):223-35. doi: 10.1016/0162-3109(95)00053-4.


It has been suggested that interleukin-4 and -5 (IL-4 and IL-5) are instrumental in the control of allergic disease. Elevated levels of IL-4 messenger RNA (mRNA) have been detected in numerous foci of atopic activity, including bronchoalveolar lavage (BAL) fluid from atopic asthmatics and skin of atopic dermatitis patients. IL-5 is important in eosinophil activation, which is a common feature of atopic disease. IL-5 mRNA has been detected in BAL fluid from both atopic and non-atopic asthmatics, indicating that IL-5 may be a common feature of the two disease states. Production of IL-4 and IL-5 by T cells appears to be associated with a high affinity cyclic AMP (cAMP) phosphodiesterase (PDE). This study was designed to compare the effects of PDE inhibitors Ro20-1724 and theophylline on (1) the mitogenic response of peripheral blood mononuclear cells from atopic and non-atopic individuals and (2) secretion of IL-4 and IL-5 by TH(2) cells after activation with PMA and anti-CD3. Both Ro20-1724 and theophylline inhibited proliferation of PBMC in a dose-dependent manner. There was no significant difference between proliferation of PBMC from atopic versus non-atopic donors, but Ro20-1724, a specific PDE IV inhibitor, was more potent at a concentration of 10(-5)M than theophylline in suppressing lymphocyte proliferation. Similarly, both PDE inhibitors suppressed secretion of IL-4 and IL-5 from TH(2)-like cell lines in a dose-dependent manner. In conclusion, as Ro20-1724 and theophylline inhibit proliferation of PBMC and secretion of IL-4 and IL-5 from human TH(2) cell lines, the development of a selective cyclic nucleotide PDE IV inhibitor may provide a promising new approach for asthma prophylaxis.

MeSH terms

  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / pharmacology
  • Adolescent
  • Adult
  • Cells, Cultured
  • Growth Inhibitors / pharmacology*
  • Humans
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / metabolism*
  • Interleukin-5 / antagonists & inhibitors
  • Interleukin-5 / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Th2 Cells / drug effects
  • Th2 Cells / enzymology*
  • Th2 Cells / metabolism*
  • Theophylline / pharmacology


  • Growth Inhibitors
  • Interleukin-5
  • Phosphodiesterase Inhibitors
  • Interleukin-4
  • 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
  • Theophylline