Phosphodiesterase type 4 inhibitors, but not glucocorticoids, are more potent in suppression of cytokine secretion by mononuclear cells from atopic than nonatopic donors☆☆☆★

Glucocorticoids up‐regulate constitutive interleukin‐10 production by human monocytes

“…To this end, we have analysed, for the first time, the effect of GCs on the constitutive production of this cytokine by ex vivo unstimulated cells. Other previous works had analysed the effect of these hormones on IL‐10 secretion induced by polyclonal activators [14–19]. Our data show that the synthetic steroid Dex, up‐regulates the spontaneous production of IL‐10 by unstimulated human monocytes, whereas this treatment has no effect on the basal production of IL‐10 by peripheral T or B lymphocytes.…”

“…In contrast, data concerning the role of GCs in regulating the production of anti‐inflammatory cytokines are contradictory. Most published studies have shown that induced IL‐10 expression is either not affected or positively affected by GCs [14–17], whereas a few have reported a down‐regulatory effect [18, 19]. In vivo , a positive correlation between steroid treatment and increased plasma levels of IL‐10 has been found in cardiopulmonary by‐pass [20], endotoxemia [21], multiple sclerosis [22] and rheumatoid arthritis [23].…”

Anti-Inflammatory Activity of Parthenolide-Depleted Feverfew (Tanacetum parthenium)

“…PD-Feverfew did not inhibit NF-κB suggesting that the inhibition of cytokine release was NF-κB-independent. PD-Feverfew was found to effectively inhibit phosphodiesterases 3 (PDE3) and 4 (PDE4), and inhibition of PDE3 or PDE4 has been shown to block the stimulated release of proinflammatory cytokines from human peripheral blood mononuclear cells (Yoshimura et al, 1997;Crocker et al, 1998). Furthermore, topical administration of PD-Feverfew was also found to reduce the levels of the cytokines, IL-2, TNFa, and IFNγ in inflamed murine tissue ( Figure 4B).…”

Preferential inhibition of human phosphodiesterase 4 by ibudilast

“…The proliferative response of mononuclear cells of atopic donors is more sensitive to PDE4 inhibition (Banner et al, 1995). PDE4 inhibitors, but not glucocorticoids, were more potent at suppressing TNFa release from mononuclear cells of atopic donors compared with normal donors, suggesting that they may have a greater therapeutic potential over steroids in the treatment of allergic diseases (Crocker et al, 1998). Taken together, the present study supports the hypothesis that the antiinflammatory and anti-allergic property of ibudilast from PDE4 inhibition may have contributed significantly to its improved clinical efficacy in the treatment of ocular allergy.…”