Medications that inhibit interleukin-1beta (IL-1beta), which is a molecule that simulates the immune system, is given to rheumatoid arthritis patients. These patients are 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. It also uncovers a critical new role for IL-1beta as the body’s independent early warning system for bacterial infections. Their study was published in Science Immunology.
Being better equipped to design more personalized and targeted therapies for auto immune diseases occurs, when more is known about each step in the body’s immune response to bacterial infections. IL-1beta stimulates an immune response and calls white blood cells to the site of an infection, so that they can engulf and clear away any invading pathogens. It has been believed by the scientific community that only the body itself could cleave and activate IL-1beta, by employing a cellular structure known as the inflammasome. Through experiments using cell cultures and mouse models of infection, Victor Nizet, MD, professor of pediatrics and pharmacy at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, found that SpeB, an enzyme secreted by strep bacteria, also cleaves and activates IL-1beta, triggering a protective immune response.
This might explain why some of the more invasive and flesh-eating strep strains have a genetic mutation that blocks SpeB production. It helps them to avoid tripping the alarm and setting off an immune response. Researchers hypothesize that for less invasive strains, the resulting immune response may wipe out competing bacteria and help strep establish a foothold in the body.
The human immune system can quickly recognize and respond to bacterial infections, and sometimes this reaction can go overboard, leading to autoimmune diseases, such as rheumatoid arthritis. A person’s own immune system attacks “self” proteins instead of only those foreign invaders. It was found by the researchers that those patients receiving anakinra were more than 300 times more likely to experience invasive, flesh-eating strep infections than patients not taking the drug.
Strep strains can progress to invasive infection even while producing SpeB, which goes unnoticed by the immune system. This brings to the front the findings of IL-1beta’s importance as an early warning system that’s triggered not only by the host, but also directly by bacterial enzymes, essentially taking out the middleman. They believe this capacity for direct pathogen detection represents IL-1beta’s original role in immunity, going all the way back in evolution to simpler animals, such as fish.
The fact that they now know this patient population is at higher risk, and why, just means we can take simple steps as close monitoring and prophylactic antibiotics to prevent it from happening.
-Dr Fredda Branyon