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

• Published in: Immunopharmacology 1996-03, Vol.31 (2-3), p.223-235
• Main Authors: Crocker, I.Caroline, Townley, Robert G., Khan, Manzoor M.
• Format: Article
• Language: English
• Subjects: 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone - pharmacology; Adolescent; Adult; AIDS/HIV; Biological and medical sciences; Cells, Cultured; Cytokines; Growth Inhibitors - pharmacology; Humans; Immunomodulators; Interleukin-4; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - secretion; Interleukin-5; Interleukin-5 - antagonists & inhibitors; Interleukin-5 - secretion; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - drug effects; Medical sciences; Pharmacology. Drug treatments; Phosphodiesterase inhibitors; Phosphodiesterase Inhibitors - pharmacology; Proliferation; Th2 Cells - drug effects; Th2 Cells - enzymology; Th2 Cells - secretion; TH2 human cell lines; Theophylline - pharmacology
• ISSN: 0162-3109
• 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 TH2 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 10−5M than theophylline in suppressing lymphocyte proliferation. Similarly, both PDE inhibitors suppressed secretion of IL-4 and IL-5 from TH2-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.