Protection from T Cell-Mediated Murine Liver Failure by Phosphodiesterase Inhibitors

摘要: Injection of the T cell mitogens concanavalin A (Con A) into nonsensitized or staphylococcal enterotoxin B (SEB) intod-galactosamine (GalN)-sensitized mice is known to cause fulminant liver failure via a cytokine response syndrome with tumor necrosis factor-α (TNF) as pivotal mediator. We examined in vivo whether phosphodiesterase (PDE) inhibitors motapizone (PDE3-selective) and rolipram (PDE4-selective) affected release hepatic injury after activation. Both well dose-dependently (0.1–10 mg/kg) attenuated systemic TNF interferon-γ initiated by injection Con (25 SEB (2 mg/kg). Although interleukin-4 production was not decreased rolipram, circulating levels interleukin-10, however, were significantly increased PDE inhibitor-treated compared controls. Associated suppression central mediator TNF, protected from model. Moreover, combined administration plus at doses which ineffective when given alone completely GalN/SEB toxicity. These data demonstrate that effectively attenuate an inflammatory strongly suggest therapeutic potential anti-inflammatory drugs cell-related disorders. conclude cAMP-elevating shift balance cell-derived cytokines proinflammatory enhanced factor release, thus protecting TNF-mediated failure.