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New anti-inflammatory drugs might help avoid side effects of steroids
Date:10/25/2011

off the invading microbes. In the case of autoimmune diseases and cancer tumors, the cytokines are released inappropriately, causing inflammation that serves no immune function. Steroids help counter this inflammation.

However, Evans, a Howard Hughes Medical Institute Investigator, points out that steroids can produce serious side effects, including immune system suppression, high blood sugar, muscle weakness and glaucoma that limit their use.

"To reduce these complications we wanted to know whether there are missing links in the steroid chain of suppression that can help us reduce some of the side effects," Evans says. "To figure out the chain of events, at the molecular level, we teamed with Verma and together uncovered the hidden link that may lead to new drugs targets."

The scientists found a potential new target by genetically modifying a strain of mice to silence the gene that produces the p53 tumor suppressor protein. As a result, glucocorticoids were ineffective at countering the inflammation response in the mice, meaning that p53 is key gear in the cellular mechanism that allows the steroids to suppress inflammation.

Due to p53's role in suppressing cancer, scientists have already identified a number of other proteins capable of altering its activity. Based on their findings, the researchers think these proteins also might be effective as anti-inflammatory drugs that operate by stimulating p53 activity. This could offer the possibility of powerful anti-inflammatories without the nasty side effects of steroids.

Their results also suggest that some cancer patients, who have a genetic mutation in their tumors that results in abnormal p53 activity, might be suffer through the side effects of steroids for no reason.

"If p53 is required for glucocorticoids to work, yet their tumor cells aren't producing p53 normally, they may be receiving steroid treatment and dealing with the ramifications with no thera
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Contact: Andy Hoang
Ahoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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