Prostaglandins of the E series (
PGE1,
PGE2) have well-described immunosuppressive (antiinflammatory) as well as
vasodilator (pro-inflammatory) actions. The net effect on an acute inflammatory response would depend on the dose, timing, and site of action. Egg phosphatidyl
liposomes are novel
drug delivery vehicles that can alter the in vivo disposition of
PGE1. The purpose of this study was to explore the therapeutic potential of
PGE1, with or without
liposome encapsulation, on the systemic inflammatory response evoked by
endotoxin following
trauma. Anesthetized pigs received a
soft tissue injury +
hemorrhage, and fluid
resuscitation after 1 h. In one series, whole blood was incubated with
PGE1 (0, 40, or 200 micrograms/mL) and
Escherichia coli endotoxin (LPS; 0, 1, 5, or 10 micrograms/mL) in vitro and neutrophil CD18 adherence receptor density was measured with immunomonitoring. In another series, LPS (5 micrograms/kg) was administered 3 days following
trauma to animals pretreated with either
phosphate-buffered saline (PBS) +
PGE1 (62 ng/kg/min x 40 min, 2.5 micrograms/kg total, n = 8), PBS (n = 12),
liposomes alone (Lipo, n = 10) or
liposome-encapsulated
PGE1 (Lipo +
PGE, n = 7). This
PGE1 dose had minimal effects on blood pressure in baseline conditions. Hemodynamics, cell differential counts, plasma
cortisol, and plasma
tumor necrosis factor (TNF) were measured for 3 h post-LPS. LPS in vitro caused a dose-related increase in neutrophil CD18 expression that was not altered by < 200 micrograms/mL
PGE1 before or after
trauma.(ABSTRACT TRUNCATED AT 250 WORDS)