DIFFERENTIAL SUSCEPTIBILITY OF RHESUS-MONKEYS TO HIGH-DOSES OF ENDOTOXIN

We investigated susceptibility of rhesus monkeys (Macaca mulatta) to E scherichia coil endotoxin (ETX) in two ways, We infused 8 monkeys (gro up A) with various doses of ETX (1.0-7.5 mg/kg) to assess the effect o f dose on shock severity; and we infused 6 monkeys (group B) with 1.0 mg ETX/kg to test biological variability to ETX challenge, Controls we re 7 saline-infused monkeys, Systolic pressure, heart rate (HR), tempe rature, plasma ETX and inflammatory markers - tumor necrosis factor-al pha (TNF), interleukin-1 (IL-1) and IL-6 - were quantified before and at 1.5, 2.5, 6 and 26 h after infusion, The highest plasma concentrati ons of ETX (at 1.5 h) - < 8% that infused - correlated well with the i nfused doses, ETX elicited hypotension and increases in HR in all monk eys, Fever did not occur, The degree of hypotension and increase in HR and death did not correlate with ETX dose (or plasma ETX concentratio ns). The response of inflammatory cytokines to ETX was greater in nons urvivors than in survivors, The observed low mortality rate (4/14) sug gests that rhesus monkeys are rather resistant to high endotoxin conce ntrations similar to baboons but unlike humans or chimpanzees, The lac k of correlation between ETX dose and shock severity suggests that the re is a critical ETX concentration in each animal that leads to contro llable or uncontrollable cytokine elevation in plasma, with reversible or irreversible shock, and resulting survival or death.