However, elderly men and frail women who showed increased levels of inflammatory diseases and weakened defenses against infections tended to have lower levels of the first two cytokines, which are protective, and higher levels of IL-17, which is linked to inflammation. That imbalance, the researchers found, began in late middle age.
They then set out to find a drug that could raise IL-2 and IFN-gamma and either have no effect on IL-17 or lower it.
"We now had a profile in humans that we could take to test tubes to say, 'Does this drug have a desirable effect?'" Goetzl said. "Our job was to find a therapy that not only works, but does so at a dose range with no side effects."
The team focused on three classes of drugs, among them the one that includes lenalidomide a derivative of thalidomide which is undergoing a renaissance, Goetzl said.
First introduced in the late 1950s as a sedative, thalidomide was never approved in the United States, but was withdrawn from the world market in 1961 after causing severe birth defects in infants whose mothers took the drug to reduce nausea during pregnancy.
In recent years, however, lenalidomide has been found to be an effective co-therapy for some cancers, particularly multiple myeloma and kidney tumors, as well as leprosy, at doses of 5 mg to 20 mg per day. Those cancers are tied to a drop in IL-2, the main cytokine that Goetzl's team had linked to declines in aging immune systems.
In this study, the team tested the drug in healthy seniors, each of whom were matched in race, gender and national origin to a healthy young adult participant. They found that extremely low levels of lenalidomide 0.1 μM optimally stimulated IL-2 production in the young people
|Contact: Kristen Bole|
University of California - San Francisco