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 lo ng-term survival in a mouse model of endotoxemia and for its effects o n endotoxin-induced suppression of human leukocyte migration. Swiss We bster mice were simultaneously rendered endotoxemic with a single intr aperitoneal injection of 800 mu g 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, 0.01 mg/kg in 0.0 4 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-resuscita ted control group: 0.04 ml saline s.c.). Octreotide was continued with or without supplemental s.c. fluid resuscitation (0.4 ml saline) at e ight hour intervals for either twenty-four or forty hours. There was n o statistical significance to differences in long-term survival betwee n comparable groups of octreotide treated vs saline treated animals du ring the entire fourteen day period of observation. Fluid resuscitatio n 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 conce ntrations 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 octreotid e treatment failed to improve long-term survival in mice with endotoxe mia and did not alter endotoxin-induced suppression of leukocyte migra tion.