Ricin Exposure in Mice Induces an Inflammatory Response Leading to Anemia and Kidney Failure

Bruce Magun, Ph.D.
Oregon Health Sciences University
R01ES08456

Background: In recent years, ricin has gained great notoriety as a possible biological warfare agent and terrorist weapon. Its significance is partly related to its potential wide availability. Annually worldwide, one million tons of castor beans are processed to make castor oil. About 5% of the waste from this process is ricin. Ricin is stable to temperature extremes and is very toxic by several routes of exposure including inhalation, ingestion or injection. As little as 500 micrograms, about the size of a pin-head, of ricin can be lethal depending upon the route of exposure. Clinical symptoms are severe inflammation and multi-organ failure. Respiratory exposure causes severe lung and airway inflammation and necrosis along with fluid accumulation. Ingestion causes severe gastrointestinal bleeding and liver, spleen, and kidney necrosis. There is no known antidote for ricin poisoning.

Advance: Previous studies by this NIEHS-supported researcher have shown that ricin damages ribosomal RNA inhibiting protein translation along with stimulating stress-activated protein kinases. The current study illustrates that ricin activates members of the mitogen activating protein kinase family, induces expression of proinflammatory genes, and when administered to mice, causes a severe inflammatory response. The treated mice developed a condition that shares most of the characteristics of human hemolytic uremic syndrome, including anemia, loss of platelets, renal failure, etc. Most cases of hemolytic uremic syndrome occur after an infection of the digestive system by Escherichia coli bacterium, which is found in contaminated foods like meat, dairy products, and juice. Some people have contracted HUS after swimming in pools or lakes contaminated with feces.

Implications: This report shows that ricin administration in mice could be used not only as a model to study the inflammatory response, but also to study the pathogenic mechanisms of hemolytic uremic syndrome in humans. This model may aid the development of therapeutic strategies for treating the life-threatening consequences of hemolytic uremic syndrome and to discover potential treatments for ricin toxicity.

Citation: Korcheva V, Wong J, Corless C, Iordanov M, Magun B. Administration of ricin induces a severe inflammatory response via nonredundant stimulation of ERK, JNK, and P38 MAPK and provides a mouse model of hemolytic uremic syndrome. Am J Pathol. 2005 Jan;166(1):323-39.