Ann Arbor---Researchers at the University of Michigan and the University of Freiberg in Germany have demonstrated that blocking a substance the body normally produces to help fight bacteria shows great promise in animal studies as a potential treatment for the highly lethal disease, sepsis.
The findings are published in the July 1999 issue of Nature Medicine.
Sepsis is a bacterial infection of the blood or body tissues that kills half of the hundreds of thousands of people who get the disease each year in the United States.
Investigators found that when they blocked C5a, a protein product that is normally activated by the immune system, they were able to provide a significant degree of protection in sepsis-induced rats. C5a is a product of the mammalian complement system---a complex system of proteins and plasma that has powerful immune functions. C5a normally binds to certain white blood cells, called neutrophils, stimulating them to kill bacteria.
Earlier studies had shown that in sepsis an excess of C5a is produced, causing the neutrophils to become overstimulated and paralyzing many of their defensive functions. In essence, sepsis causes the body's own immune system to disarm its ability to fight the disease.
Researchers, led by Peter A. Ward, M.D., chair of the Department of Pathology in the University of Michigan Health System, found that septic rats injected with an immunoglobulin (IgG) antibody against C5a had powerful protection against sepsis. In the group of rats treated with the antibody against C5a, more than half survived. By contrast, in a second group treated with standard immunoglobulin, only 5 percent survived.
"This study reveals that in experimental sepsis, the system that produces
protective mediators is overstimulated, leading to profoundly harmful
consequences," says Ward. "If this is also the case in humans with sepsis, there
could be obvious implications for a new therapeutic approach for the treatment
Contact: Peter Barkey
University of Michigan