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

Abstract

5 These results show that combined inhibition of the type 3 and 4 PDE isoenzymes in HPBM from normal subjects has a greater antiproliferative effect than inhibition of the type 4 isoenzyme alone. In addition these data indicate that the proliferative response of HPBM from AD subjects is more sensitive to PDE 4 inhibition than the proliferation of HPBM from normals.

Effects of theophylline and rolipram on leukotriene C4 (LTC4) synthesis and chemotaxis of human eosinophils from normal and atopic subjects

“…However, maximal inhibition of chemotaxis with RS25344 attained only 40% whereas maximal inhibition with rolipram was 70-80% and with theophylline 80-90%. In view of recent data demonstrating that PDE4 inhibitors are more potent in suppressing proliferation (Banner et al, 1995) and IL4-synthesis (Chan et al, 1993a) by mononuclear cells obtained from atopic subjects than from normal individuals, we have compared the effects of rolipram and theophylline on LTC4 synthesis and chemotaxis of eosinophils obtained from normal and atopic individuals. As shown in Table 1, eosinophil functions were suppressed by the PDE inhibitors in a similar fashion.…”

“…An inhibitory effect of theophylline on leukocyte LTC4 generation has recently been noted by Kristiansson et al (1994). Secondly, suppression of eosinophil chemotaxis in vitro would provide a rationale for the inhibition of eosinophilic airway inflammation by PDE inhibitors in vivo (Teixera et al, 1994;Banner & Page 1995). Recently, it has been demonstrated that cyclic AMP-elevating agents, including the selective PDE4 inhibitors RS 25344 (Kaneko et al, 1995) and Way PDA-641 (Tanimoto et al, 1994), may inhibit eosinophil migration in vitro.…”

A Biochemical and Functional Assessment of Monocyte Phosphodiesterase Activity in Healthy and Asthmatic Subjects

“…Indeed, there is a concAMP in monocytes. This increased PDE3 activity siderable body of evidence of increased PDE4 inwas not due to differential contamination of monohibitor sensitivity observed in inflammatory cell cytes from asthmatic subjects by platelets (which are populations obtained from some 8,10,22 but not all 9,29 rich in PDE3) since microscopic examination of our subjects with atopic dermatitis. This discrepancy monocyte cell preparation showed that there were might relate to differences in patient populations, very few platelets present.…”

“…previous studies demonstrating a lack of effectiveness Taken alongside other changes in PDE3 and PDE4 of siguazodan upon proliferation of mononuclear activity being different from those observed in patients cells, proliferation of T cell clones and cytokine release with atopic dermatitis, this suggests that the changes from T cell clones. 10,[35][36][37] Nevertheless, PDE3 is clearly we have observed are unlikely to just be due to the expressed in these cells as assessed biochemically. 9 presence of atopy in our asthmatic sample.…”

Selective phosphodiesterase inhibitors modulate the activity of alveolar macrophages from sensitized guinea-pigs

“…Indeed, the selective PDE3 inhibitor milrinone elicits a moderate inhibition of arachidonate release from these cells [6] and appears to synergize with inhibitors of PDE4 to reduce proliferation [7]. In macrophages, in the presence of the adenylyl cyclase activator, prostaglandin E2 (PGE2), PDE3 inhibitors are as effective as PDE4-selective drugs in the inhibition of tumour necrosis factor-α release [8].…”