Actions of prostaglandin E1 on lipopolysaccharide-evoked responses in vivo and in vitro following resuscitated trauma.
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)
Stewart
R M
RM
Department of Surgery, University of Tennessee, Memphis 38163, USA.
Fabian
T C
TC
McGinty
M P
MP
Fabian
M J
MJ
Proctor
K G
KG
D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D003238:Connective Tissue / Q000473:pathology*; D006470:Hemorrhage / Q000473:pathology*; D008070:Lipopolysaccharides; D008081:Liposomes; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000473:pathology; D012772:Shock, Septic / Q000188:drug therapy* / Q000473:pathology; D013552:Swine
D008070:Lipopolysaccharides; D008081:Liposomes; D000527:Alprostadil