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See Inside September / October 2009

Inflammation Brings on the Blues

Our immune system may mean well, but it might also cause depression

As if being stuck sick in bed wasn’t bad enough, several studies conducted during the past few years have found that the immune response to illness can cause depression. Recently scientists have pinpointed an enzyme that could be the culprit, as it is linked to both chronic inflammation—such as that found in patients with coronary heart disease, type 2 diabetes and rheumatoid arthritis—and depressive symptoms in mice.

In the new study, immuno­physiologist Keith Kelley and his colleagues at the University of Illinois exposed mice to a tuberculosis vaccine that produces a low-grade, chronic inflammation. After inocu­lation, production in the mice brains of an enzyme called IDO, which breaks down tryptophan, spiked. The animals exhibited normal symptoms of illness such as moving around and eating less. Yet even after recovering from the physical illness induced by the vaccine, they showed signs of depression—for example, struggling less than control mice to escape from a bucket of water. Surprisingly, their listlessness was solved relatively simply. “If you block IDO, genetically or pharmaceutically, depression goes away” without interfering with the immune response, Kelley explains.

The research makes a solid case that the immune system communi­cates directly with the nervous system and affects important health-related behaviors such as depression. The findings could bring relief to patients afflicted with obesity, which leads to chronic inflammation, as well as to cancer patients treated with radiation and chemotherapy drugs that produce both inflammation and depression. “IDO is a new target for drug compa­nies to aim for, to treat patients with both clinical depression and systemic inflammation,” Kelley says.

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