Spotlight on Research 2007

April 2007 (historical)

Study Finds Determinant of Allergic Reaction Anaphylaxis

For some people, being stung by a bee is not only painful, it is life-threatening. They develop a severe allergic response, called anaphylaxis, that can cause shock and serious trouble with breathing. Bee stings and peanut allergies are well-known anaphylaxis triggers, but any allergen-be it a food, drug, chemical or type of pollen-can set off this potentially deadly reaction.

No one knows exactly why one person who is allergic sneezes and gets itchy eyes while another person has severe anaphylaxis, but recent work at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) sheds some light on how their immune systems might differ. Juan Rivera, Ph.D., along with a team of researchers at the NIAMS Molecular Immunology and Inflammation Branch and colleagues at the National Institute of Diabetes and Digestive and Kidney Diseases, reported in the journal Immunity that mice with high levels of a molecule called sphingosine-1-phosphate (S1P) in their blood were very susceptible to anaphylaxis.

Dr. Rivera says, "Our findings about S1P and anaphylaxis were unexpected. We set out to address what causes mast cells to respond to an allergy-stimulus in vivo." Mast cells are white blood cells that release allergen-fighting substances, such as histamine, during an allergic reaction. "We were using mice that could not produce sphingosine kinase 1 or sphingosine kinase 2," he said, referring to two proteins (also called Sphk1 and Sphk2) that mast cells activate when confronted by allergens. "When we compared their responses with those of normal mice, we found that anaphylaxis severity correlated with circulating S1P levels."

The team's mouse study resulted in other findings, as well. They learned that Sphk2 is required for producing S1P in mast cells, whereas S1P circulating in the bloodstream is dependent on Sphk1. They also learned that Sphk2 is necessary for calcium influx and protein kinase C activation, two critical elements involved in the mast cells' release of their allergen-fighting substances.

In humans, the circulating levels of S1P may vary from person to person. These levels might be influenced by a variety of factors, including genetic makeup and dietary factors. Dr. Rivera's team is currently considering a project to study S1P in people who have a history of anaphylactic shock. If levels of the molecule in humans can predict who is at risk for anaphylaxis, S1P might someday have a role as a diagnostic tool.

The mission of the NIAMS, a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at

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Olivera A et al. The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity 2007;26:287-297.