Pentoxifylline inhibits the synthesis and IFN-γ-inducing activity of IL-18

Abstract

SUMMARYThe effect of phosphodiesterase-inhibiting anti-inflammatory drug pentoxifylline (PTX) on LPS-induced IL-18 synthesis and IL-18-mediated IFN-g-induction were investigated. In a dose-dependent manner PTX inhibited production of IL-18 in LPS-treated cultures of murine spleen cells and bone marrowderived 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 LPSinjected animals. Synergistic induction of IFN-g 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-g induction. These results suggest that interference with IL-18 synthesis and IFN-g-inducing activity might contribute to anti-inflammatory actions of PTX.

Modulation of radiation-induced oral mucositis by pentoxifylline: Preclinical studies

“…PTX is a methylxanthine derivative with rheological effects, which is widely used to treat peripheral vascular diseases [22] and also has significant anti-inflammatory activity [23][24][25][26].…”

Pentoxifylline Prevents Spontaneous Brain Ischemia in Stroke-Prone Rats

“…This newly described pharmacological effect can be ascribed to an inhibition of the functional responses of circulating mononuclear phagocytes, neutrophils, and T lymphocytes and the decreased synthesis of several proinflammatory cytokines (Dong et al, 1997;Neuner et al, 1997;Marcinkiewicz et al, 2000;Bahra et al, 2001;Laurat et al, 2001;Samardzic et al, 2001). Studies of the anti-inflammatory effects of PTX in vivo have focused attention on tissue injury after ischemia.…”

Pentoxifylline Explores New Horizons in Treatment of Hashimoto Thyroiditis

“…In animal models of autoimmune thyroiditis, Interleukin 12 (IL-12) has been demonstrated to be another initiator of Th-1 mediated response against thyrocytes [50]. Considering the issue that IL-12 induces further expression of IFN-γ, IL-12 can be the primary initiator of the disease process [50,51]. PTX also suppresses IL-12 inducted expression of IFN-γ [51].…”