COMPARISON OF THE EFFICACY OF PENTOXIFYLLINE AND ALBIFYLLIN (HWA-138)ON ENDOTOXIN-INDUCED CYTOKINE PRODUCTION, COAGULATION DISTURBANCES, AND MORTALITY

We have evaluated two different xanthine derivatives, pentoxifylline ( POF) and albifyllin (HWA), in rat endotoxemia for their ability to red uce 1) cytokine formation, 2) coagulation disturbances, and 3) mortali ty. The animals were injected with lipopolysaccharide (LPS) (15 mg/kg i.p.) and received HWA or POF (25, 50, or 100 mg/kg) or saline 30 min before LPS administration. The plasma tumor necrosis factor levels wer e significantly reduced and in a similar manner by pretreatment with H WA or POF in vivo as well as in vitro. Neither the coagulation disturb ance nor the characteristic leukopenia that follow an LPS challenge we re significantly influenced by the xanthine derivatives. At a dose of 100 mg/kg, the 6 day mortality was significantly reduced by HWA to 36% but only attenuated by POF to 55% as compared to 80% in the control g roup. The similar effect of both agents on cytokine formation and coag ulation disturbances indicate that, at least to a substantial degree, other mechanisms may account for the significant protection of rats ag ainst endotoxin-induced mortality by HWA only. HWA 138 may, therefore, be a new powerful agent against endotoxin-related disorders and morta lity.