Could isoenzyme-selective phosphodiesterase inhibitors render bronchodilator therapy redundant in the treatment of bronchial asthma?

Differential effect of phosphodiesterase 4 inhibitors on the proliferation of human peripheral blood mononuclear cells from normals and subjects with atopic dermatitis

“…The type 4 PDE isoenzyme appears to be the main PDE isoenzyme present in inflammatory cells and has been characterized in T-lymphocytes, eosinophils, neutrophils, monocytes, basophils, mast cells and endothelial cells (Souness et al, 1991;Giembycz, 1992), although the type 3 PDE isoenzyme has also been identified in human peripheral blood lymphocytes (Thompson et al, 1976;Robicsek et al, 1991).…”

“…This family of enzymes is presently known to exist in at least 7 different isoenzyme forms (Giembycz & Kelly, 1994) which are characterized by a variety of criteria including their sensitivity to different inhibitors (Nicholson & Shahid, 1993). The predominant PDE isoenzyme in most inflammatory cells is PDE 4 (Giembycz, 1992). However, both the type 3 and 4 PDE isoenzymes have been characterized (Thompson et al, 1976;Takemoto et al, 1978;Robicsek et al, 1991) and are known to control cyclic AMP breakdown in human T-lymphocytes (Schudt et al, 1992).…”

Acute versus chronic administration of phosphodiesterase inhibitors on allergen‐induced pulmonary cell influx in sensitized guinea‐pigs

“…The type IV PDE isoenzyme has been characterized in eosinophils, Tlymphocytes, neutrophils, monocytes, basophils, mast cells and endothelial cells (Souness et al, 1991;Giembycz, 1992). Inhibition of the type IV isoenzyme has been shown both in vivo and in vitro to be capable of modifying the behaviour of these cells in terms of their migration and also their mediator release (Torphy & Undem, 1991).…”

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“…Of these, PDE3, PDE4 and PDE7 appear to be most important for the regulation of cAMP in different cell types. However, most cells implicated in the pathogenesis of inflammation express one or more representatives of the PDE4 isoenzyme family which are primarily or even exclusively responsible for the degradation of cyclic AMP in these cells (see Torphy & Undem 1991, Giembycz 1992. Accordingly, PDE4 inhibitors are capable of increasing cyclic AMP levels and inhibiting various functional responses in most leukocytes that are considered pro-inflammatory (reviewed in Torphy & Undem 1991, Giembycz 1992.…”

“…However, most cells implicated in the pathogenesis of inflammation express one or more representatives of the PDE4 isoenzyme family which are primarily or even exclusively responsible for the degradation of cyclic AMP in these cells (see Torphy & Undem 1991, Giembycz 1992. Accordingly, PDE4 inhibitors are capable of increasing cyclic AMP levels and inhibiting various functional responses in most leukocytes that are considered pro-inflammatory (reviewed in Torphy & Undem 1991, Giembycz 1992. For example, the elevation of cyclic AMP in eosinophils has been associ-ated with inhibition of functions including the respiratory burst, degranulation, aggregation and lipid mediator production ( Teixeira et al 1996 and references therein).…”