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.