摘要：

SUMMARYInhibitors of cyclic nucleotide phosphodiesterases are known to suppress lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-α) production in vitro in human monocytes. The most potent of these have selectivity for type IV PDEs, suggesting that this class of PDE is the major type involved in the regulation of human TNF-α production. Using compounds of two distinct chemical structural classes, a quinazolinedione (CP-77 059) and a 4 arylpyrrolidinone (rolipram). we show here that PDE-IV-specific inhibitors are also potent in suppressing LPS-induced TNF-α production in vitro in sodium periodate-elicited murine macrophages (IC50s of 1 and 33, respectively). We then report the in vivo anti-inflammatory effect of PDE-IV inhibition in five murine models of inflammation: (i) elevation of serum TNF-α induced by a subtethal LPS injection; (ii) LPS-induced endotoxic shock; (iii) LPS/galactosamine-induced endotoxic shock; (iv) carrageenan-ind

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