Why Steroids Fail Many Lupus Patients

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Steroids are among the most commonly used treatments for people who have lupus (systemic lupus erythematosus), yet many patients do not respond to these drugs. Now researchers with the Baylor Research Institute (BRI) in Dallas say they believe they know why steroids fail.

Corticosteroids, also known as steroids or cortisone, are synthetic drugs designed to perform like the hormones produced by the adrenal glands, especially cortisol. Steroids are used to treat autoimmune conditions like lupus to decrease swelling, tenderness, pain, and warmth associated with the inflammation that is characteristic of the disease. Prednisone is the most commonly prescribed steroid for lupus, while some physicians prescribe prednisolone or methyl-prednisolone for patients who have liver conditions.

In lupus and other autoimmune diseases, steroids suppress the overactive immune system and prevent it from damaging healthy tissues, which in turn cause inflammation, pain, and organ damage. Steroids kill certain immune system cells called plasmacytoid dendritic cells (PDCs) that mass produce type 1 interferon, a substance that promotes and supports lupus and other autoimmune conditions. In people with lupus, however, steroids are not as effective against PDCs as they are in other diseases.

Lupus affects an estimated 5 million people around the world, according to the Lupus Foundation of America. It most often affects women between the ages of 15 and 40. The cause is unknown, but genetics are believed to play a role.

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To uncover why steroids are less effective in patients with lupus, Virginia Pascual, MD, a researcher at Baylor Institute for Immunology Research, a component of BRI, and her colleagues, in collaboration with scientists at Dynavax in Berkeley, California, studied children with lupus. They found that two immune system proteins called toll-receptor 7 (TLR7) and toll-receptor 9 (TLR9) activate the PDCs that the steroids target, which then cancels out the effects of treatment.

Pascual notes that this finding indicates that “by blocking TLR7 and TLR9 function, we may have found a safer way to treat this debilitating disease.” One reason she says “safer way” is that large doses of steroids are necessary to treat lupus, but these drugs can cause serious side effects, including brittle bones, cataracts, weight gain, hypertension, and thin skin. In children, steroids can stunt growth.

Therefore, results of this study suggest that steroid treatment could be more effective for lupus patients if scientists can find a way to block the activity of these proteins. Pascual pointed out that their “ultimate goal is to reduce the amount of steroids these patients take because they carry a risk of serious side effects.”

To further that goal, Michael Ramsay, MD, president of BRI, explained that blocking agents for the two immune system proteins are already under development and could be ready for clinical trials in the near future. He noted that the results of this latest research on why steroids fail to help many patients “have given hope to the millions of people who suffer with lupus.”

SOURCES:
Baylor Research Institute
Lupus Foundation of America

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