PENTOXIFYLLINE INHIBITS MEDIATOR SYNTHESIS IN AN EQUINE IN-VITRO WHOLE-BLOOD MODEL OF ENDOTOXEMIA

Whole blood from 10 healthy horses was aseptically collected into hepa rin or citrate anticoagulant and incubated in vitro for 6 hr in the ab sence (saline control) or presence of 1 ng endotoxin/ml blood. Pentoxi fylline (0.1, 1, 10, or 100 mu g/ml blood) was added 1 hr before, at t he same time, or 1 hr after endotoxin. As compared to saline controls, pentoxifylline alone had no effect on mediator production, with the e xception of significantly increasing 6-keto-prostaglandin F-1 alpha co ncentration. Pentoxifylline inhibited endotoxin-induced increases in t umor necrosis factor (TNF) and interleukin-6 (IL-6) activity in a dose -related fashion, whether added before, at the same time, or after end otoxin. Pentoxifylline significantly inhibited tissue factor activity, but only when added before endotoxin. Pentoxifylline had no effect on endotoxin-induced 6-keto-prostaglandin F-1 alpha production, but sign ificantly inhibited thromboxane B-2 (TxB(2)) production. The results o f this study indicate that pentoxifylline, at blood concentrations con sistent with those achieved in vivo, has effects that may be beneficia l in the treatment of endotoxemia. (C) 1995 Wiley-Liss, Inc.