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For many, flu season is simply a nuisance. But for the elderly, it can be like navigating a minefield. With just one exposure, the virus can break through an aging immune system and make the person very sick for a long time. Now researchers at the University of California, San Francisco, have found a drug that may boost immune systems in the elderly, bringing them back to “youthful levels.”

The drug, lenalidomide, is a cousin of thalidomide, the notorious sedative that was found to cause birth defects in the 1950s. Both drugs have been used recently to treat multiple myeloma, a cancer of plasma cells in bone marrow. At much lower doses, scientists recently discovered, lenalidomide can stimulate immune responses in the elderly. The results of their study will be published in the January issue of Clinical Immunology.

“We’re looking at increasing health span versus lifespan,” says Edward Goetzl, director of allergy and immunology research at UCSF. “People have found that somewhere in their fifties, things start trickling down, and we want to keep them up.”

As we age, our immune defenses slowly become less vigilant and slower to respond to attack. A gland called the thymus shrinks, releasing fewer protective T-cells with each passing year. Researchers have found that not only do older people have fewer T-cells, but the T-cells they do have are less active, unable to migrate and patrol the body as effectively as those of young adults. Older people’s T-cells produce fewer cytokines, proteins that help the cells differentiate and proliferate through the body.

Goetzl and his colleagues hypothesized that stimulating production of cytokines could increase the proliferation of T-cells and boost aging immune systems. The team looked through libraries of existing drugs and found five that, at low doses, stimulate the immune system. After more detailed analyses, Goetzl found that only one of the five, lenalidomide, was able both to stimulate cytokine production and increase T-cell proliferation.

The team tested the drug on healthy seniors and healthy young adults. The researchers isolated T-cells from blood samples, and exposed the cells to lenalidomide. They found that the drug boosted the levels of two kinds of cytokines—IL-2, and IFN-gamma—both of which are known to stimulate T-cell production. The team found that the increased levels in seniors matched normal cytokine levels in young adults. They also observed improvements in T-cell migration in the blood samples from seniors.

It will be important to learn what kind of T-cells are producing the additional cytokines, says Janko Nikolich-Zugich, chairman of the immunobiology department at the University of Arizona and codirector of the Arizona Center on Aging. There are many subtypes of T-cells, and certain types decrease in number as we age, while the level of others remains nearly constant. “The compound could be just stimulating something that’s always been there,” says Nikolich-Zugich. “It doesn’t mean this compound might not be something useful down the line—they just have to identify what exactly it might be working on.”

Goetzl is planning a pilot study in which he will administer very low doses of the drug to patients with certain types of leukemia—ones that result in a weakened immune response similar to that seen in the elderly. He plans to monitor their immune performance and their tolerance for the drug to determine an optimal dosage. “We’re thinking of this as a pharmacological probe,” says Goetzl. “If it doesn’t end up being a drug, at least we know we can get cytokine levels up, and we know what to look for in developing new drugs.”

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Tagged: Biomedicine, immune system, drug discovery

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