Pentoxifylline inhibits the synthesis and IFN-gamma-inducing activity of IL-18
2001
Autori:
Samardžić, Tatjana S.Janković, V
Stošić-Grujičić, Stanislava
Popadić, Dusan M
Trajković, Vladimir S
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
The effect of phosphodiesterase-inhibiting anti-inflammatory drug pentoxifylline (PTX) on LPS-induced IL-18 synthesis and IL-18-mediated IFN-gamma -induction were investigated. In a dose-dependent manner PTX inhibited production of IL-18 in LPS-treated cultures of murine spleen cells and bone marrow-derived macrophages. Similarly, PTX treatment significantly reduced blood IL-18 levels and expression of spleen IL-18 mRNA in LPS-challenged mice. The inhibitory effect of PTX was specific for IL-18, since LPS-induced IL-12 p40 release was not suppressed either in splenocyte cultures or blood of LPS-injected animals. Synergistic induction of IFN-gamma by combined IL-12/IL-18 treatment was also inhibited by PTX in vitro and in vivo. Experiments with IL-12 pretreatment of splenocytes, followed by IL-18 stimulation, revealed that PTX suppressed both IL-12 and IL-18 signals responsible for IFN-gamma induction. These results suggest that interference with IL-18 synthesis and IFN-gamma -inducing activity might contribute to anti-inflammatory actions of PTX.