Octreotide does not alter endotoxin lethality in mice or endotoxin-induced suppression of human leukocyte migration.
Octreotide, a somatostatin analog, was evaluated for its effects on long-term survival in a mouse model of endotoxemia and for its effects on endotoxin-induced suppression of human leukocyte migration. Swiss Webster mice were simultaneously rendered endotoxemic with a single intraperitoneal injection of 800 micrograms E. coli Lipopolysaccharide (LPS) and treated with one of four doses of subcutaneous (s.c.) octreotide (1.0 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.04 ml saline, or 0.001 mg/kg in 0.04 ml saline) or saline alone (fluid-resuscitated control group: 0.4 ml saline s.c.; or non-fluid-resuscitated control group: 0.04 ml saline s.c.). Octreotide was continued with or without supplemental s.c. fluid resuscitation (0.4 ml saline) at eight hour intervals for either twenty-four or forty hours. There was no statistical significance to differences in long-term survival between comparable groups of octreotide treated vs saline treated animals during the entire fourteen day period of observation. Fluid resuscitation during the first forty hours following endotoxemia induction delayed death, but did not significantly improve long-term survival. In vitro work was conducted to determine the effect of octreotide on endotoxin-induced suppression of human leukocyte migration. Octreotide at concentrations ranging from 3.05 x 10(-5) Molar to 3.05 x 10(-11) Molar had no significant effect on leukocyte migration. In this study octreotide treatment failed to improve long-term survival in mice with endotoxemia and did not alter endotoxin-induced suppression of leukocyte migration.
Ogden
B E
BE
Department of Animal Care, Oregon Health Sciences University, Portland 97201.
Martin
M A
MA
Hall
A S
AS
Woltering
E A
EA
Bryant
R E
RE
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D006801:Humans; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors; D014115:Toxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*
D004731:Endotoxins; D008070:Lipopolysaccharides; D015282:Octreotide