A new study by Weill Cornell Medicine investigators has uncovered a surprising mechanism of inflammation in patients with systemic lupus erythematosus (lupus). The research reveals that immune cells known as monocytes produce an inflammatory protein called interleukin-1 beta (IL-1β) through an unconventional pathway, opening the door to potential new treatments for those who do not respond well to existing therapies. The study was published on October 7th in Immunity.

Lupus, a chronic autoimmune disease, causes the immune system to attack the body’s own tissues, leading to inflammation affecting the skin, joints, kidneys, and heart. In the United States, the prevalence of lupus is between 20 to 150 cases per 100,000 people. Although genetic factors have been identified in some patients, the exact cause remains elusive in most cases. Lupus is often characterized by overproduction of type I interferons (IFNs), proteins meant to help the body fight viruses but that can also drive harmful inflammation in autoimmune conditions.

This latest research builds on findings from 2021, where investigators found that red blood cells retained mitochondria in up to 60% of pediatric lupus patients. Mitochondrial DNA is known to trigger immune responses, and in the new study, researchers found that lupus monocytes internalizing these mitochondria-containing red blood cells produced both IFN and IL-1β. This dual production of inflammatory proteins was unexpected, given that IFN and IL-1β typically regulate each other negatively in immune responses.

“It was surprising to find co-activation of both interferon and IL-1β pathways in lupus monocytes,” said Dr. Virginia Pascual, senior author of the study and director of the Gale and Ira Drukier Institute for Children’s Health.

The study also revealed that IL-1β secretion occurs without inducing cell death—a unique characteristic that makes IL-1β an attractive target for new therapies. The researchers believe that lupus monocytes can travel throughout the body, release IL-1β, and survive in inflamed areas, further worsening the disease. These monocytes may also transform into cells that activate other components of the immune system, compounding the inflammatory response.

Looking ahead, the researchers are developing diagnostic tools to detect monocytes that produce both IFN and IL-1β, aiming to help identify patients who would benefit from therapies targeting both proteins. They hope these insights will pave the way for better treatments for lupus patients and potentially other autoimmune diseases with similar inflammatory pathways.