Unexpected target may unlock the door to fight...( Researchers induced sepsis in rats b...),Health

Researchers induced sepsis in rats by making a small perforation with a needle in the cecum (large intestine). The procedure---called cecal ligation and puncture, or CLP---causes a slow leak of the contents of the bowel, resulting in bacteria such as E.coli escaping into the body cavity. This model of sepsis and its physiological changes are very similar to those seen in human sepsis.

Three different groups of rats were studied. The first was treated with preimmune IgG immediately after CLP, while a second group received IgG antibody against C5a at the same time. In the group receiving preimmune IgG, only two of 21 rats survived more than a week, while half of the group treated with IgG antibody to C5a survived past 10 days. A third group had a different immune protein (C3) depleted and all animals died within five days.

Researchers then made another significant finding. Since this particular model of sepsis is associated with high levels of aerobic and anaerobic bacteria in the blood, investigators wondered whether rats treated with an antibody to C5a would have lower bacteria counts. Blood samples taken 96 hours after sepsis inducement showed that the rats treated with antibody to C5a had a 98 percent reduction in blood bacteria counts compared with the preimmune IgG group.

Finally, Ward and his team tested the hypothesis that the reason bacteria counts in the antibody group were so low was because the therapy preserved the capacity of neutrophils to produce hydrogen peroxide---a vital product in the ability of white blood cells to kill bacteria. They took blood samples and stimulated the neutrophils to produce hydrogen peroxide. The neutrophils taken from rats treated with antibody to C5a produced high levels of hydrogen peroxide while those taken from the preimmune IgG group showed very little production.

"It appears, at least in this experimental model, that sepsis causes activation of the complement system," says Ward. "You the get sustain
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Contact: Peter Barkey
pbarkey@umich.edu
734-764-2220
University of Michigan
29-Jun-1999