Phosphodiesterase inhibitors
Author(s): Crocker IC, Townley RG, Khan MM
Source: IMMUNOPHARMACOLOGY 31 (2-3): 223-235 MAR 1996
Document Type: Article
Language: English
Cited References: 38 Times Cited: 32
Abstract: 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(-5)M 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 TH2 cell lines, the development of a selective cyclic nucleotide PDE IV inhibitor may provide a promising new approach for asthma prophylaxis.
Author Keywords: cytokines; interleukin-4; interleukin-5; phosphodiesterase inhibitors; proliferation; TH2 human cell lines KeyWords Plus: CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; CYTOKINE PRODUCTION; ATOPIC-DERMATITIS; IGE SYNTHESIS; INVITRO; DISEASE; ASTHMA; LYMPHOCYTES; ADENOSINE; CLONES
Addresses: CREIGHTON UNIV, HLTH SCI CTR, DEPT PHARMACEUT SCI, OMAHA, NE 68178 USA
CREIGHTON UNIV, HLTH SCI CTR, DEPT MED, DIV ALLERGY, OMAHA, NE 68178 USA
Publisher: ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Subject Category: IMMUNOLOGY; PHARMACOLOGY & PHARMACY