Rheumatoid Arthritis Patients Taking Interleukin-1Beta Inhibitors Are at Much Increased Risk of Group A Strep Infections

Rheumatoid arthritis (RA) patients taking medications that inhibit interleukin-1beta (IL-1beta), a molecule that stimulates the immune system, are 300 times more likely to experience invasive Group A Streptococcal infections than patients not on the drug, according to University of California San Diego School of Medicine researchers. Their study, published August 19, 2016 in Science Immunology, also uncovers a critical new role for IL-1beta as the body's independent early warning system for bacterial infections. The article is titled “IL-1β Is an Innate Immune Sensor of Microbial Proteolysis.” "The more we know about each step in the body's immune response to bacterial infections, the better equipped we are to design more personalized, targeted therapies for autoimmune diseases -- therapies that are effective, but minimize risk of infection," said senior author Victor Nizet, M.D., Professor of Pediatrics and Pharmacy at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. IL-1beta is a molecule that stimulates an immune response, calling white blood cells (WBCs) to the site of an infection so theWBCs can engulf and clear away invading pathogens. The body first produces the molecule in a longer, inactive form that must be cleaved to be activated. The scientific community long believed that only the body itself could cleave and activate IL-1beta, by employing a cellular structure known as the inflammasome. But, in experiments employing cell cultures and mouse models of infection, Dr. Nizet and his team found that SpeB, an enzyme secreted by strep bacteria, also cleaves and activates IL-1beta, triggering a protective immune response.
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