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ARTICLE |

Liposomes Modulate Kupffer Cell Endotoxin Response

Paul Bankey, MD, PhD; Ernest Beecherl, MD; Doug Bibus, MS; Dana See; Kendra McIntyre
Arch Surg. 1995;130(12):1266-1272. doi:10.1001/archsurg.1995.01430120020003.
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Objectives:  To test the hypothesis that pretreatment with liposomes enriched with the ω3 fatty acid docosahexaenoic acid (22:6ω3) will alter the Kupffer's cell and systemic cytokine (tumor necrosis factor and interleukin-6) response to endotoxin challenge, and to demonstrate alterations in Kupffer's cell phospholipid fatty acid composition after in vivo liposome treatment.

Design:  Nonrandomized controlled laboratory investigation in Wistar rats.

Interventions:  Animals were assigned to three pretreatment groups: no liposomes; liposomes, 100 mg/kg; or liposomes, 400 mg/kg given by bolus intravenous injection with the animals under inhalation anesthesia. Eighteen hours after liposome treatment, each group was challenged with Escherichia coli lipopolysaccharide (3 mg/kg intraperitoneally in 10 mL of lactated Ringer's solution) or lactated Ringer's solution only. In a separate set of experiments, Kupffer's cells were obtained from animals pretreated with liposome, 400 mg/kg, or controls and challenged with lipopolysaccharide (1, 100, or 104 ng/mL) in vitro.

Outcome Measures:  Serum and Kupffer's cell supernatant tumor necrosis factor and interleukin-6 bioactivity, Kupffer's cell phospholipid fatty acid composition, survival, and liver histologic findings.

Results:  In vivo liposome pretreatment (400 mg/kg) resulted in significant increases in serum tumor necrosis factor and interleukin-6 levels 90 minutes after intraperitoneal lipopolysaccharide challenge (P<.05 vs no liposomes). Kupffer's cells isolated from liposome-treated animals (400 mg/kg) compared with untreated controls release significantly more tumor necrosis factor and interleukin-6 after lipopolysaccharide stimulation in vitro in a dose-dependent response (P<.05). Liposome treatment increased total polyunsaturated fatty acid, total ω3, and docosahexaenoic acid 22:6ω3 content in Kupffer's cell phospholipids compared with untreated controls. Survival 24 hours after lipopolysaccharide challenge was reduced by liposome (400 mg/kg) pretreatment (P<.05 by χ2 test). Livers from each treatment group demonstrated focal areas of hepatocyte necrosis and inflammatory cells.

Conclusion:  Liposome pretreatment increases the circulating and Kupffer's cell cytokine response to endotoxemia, increases Kupffer's cell polyunsaturated fatty acid content, and is associated with reduced survival.(Arch Surg. 1995;130:1266-1272)

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