Several factors, including uncontrolled
inflammation, gut barrier failure, and
sepsis, have been implicated in the development of
multiple organ failure. To investigate the relative importance and interrelationships among some of these factors, increasing doses of the inflammatory agent
zymosan were used to induce a systemic inflammatory state in mice. At nonlethal doses (0.1 and 0.5 mg/g
body weight),
zymosan caused injury to the intestinal mucosa, increased intestinal
xanthine oxidase activity, and promoted bacterial translocation in a dose-dependent fashion. Inhibition or inactivation of
xanthine oxidase activity was effective in reducing mucosal injury and bacterial translocation when
zymosan was injected at 0.1 mg/g but not at 0.5 mg/g
body weight. At a dose of 1 mg/g, the lethal effects of
zymosan appeared to be related to gut-origin
sepsis, since
cefoxitin (1 mg/g) reduced the seven-day mortality rate from 100% to 20% (p less than 0.01). However, at a
zymosan dose of 2 mg/g,
antibiotics did not improve survival.
Zymosan thus induced gut barrier failure and systemic
infection in a dose-dependent fashion. Additionally, the mechanism of
zymosan-induced bacterial translocation and the relationship of gut-origin
sepsis to survival appeared to be related to the magnitude of the inflammatory insult (the dose of
zymosan).