Paving the way towards a new anti-inflammatory agent

Hudson Institute researchers provide new insights into how the IL-37 protein blocks inflammation—emphasising the potential for a novel treatment in the fight against a plethora of inflammatory diseases.

IL-37 is considered a fairly new drug candidate for the treatment of inflammatory diseases that carries great promise, but its development has been slowed down by the incomplete understanding of how IL-37 functions.

Chronic inflammatory and autoimmune diseases are rife in Western society. One in nine Australians have asthma, one in 12 have psoriasis, one in 250 have inflammatory bowel disease and one in 1000 have lupus—just a few examples from the vast array of inflammatory conditions.

Just ten years ago—in terms of scientific research, very recently—the Interventional Immunology in Early Life Diseases group at Hudson Institute discovered that the IL-37 protein exerts a powerful anti-inflammatory effect in the body.

What did the team discover?

Dr Ina Rudloff, along with Associate Professor Claudia Nold and Professor Marcel Nold, led a study published in Cells which has broadened the knowledge around the mechanisms IL-37 employs to prevent inflammation.

Dr Ina Rudloff, Postdoctoral Scientist in the Interventional Immunology in Early Life Diseases group.

The team discovered, using both pre-clinical and in vitro models, that IL-37 inhibits inflammation by targeting multiple steps required for the production of proteins such as IL-1β, which promote inflammation in the body.

“Our study provides new information on how IL-37 can inhibit inflammation and makes a compelling case for investigations into IL-37 as a therapeutic for inflammatory diseases,” said Dr Rudloff.

IL-1β is first produced in an immature form—meaning it is inactive—and needs to be processed (to become mature and active) by a complex called the inflammasome, which consists of several proteins.

The team found that IL-37 not only inhibits the production of immature IL-1β, but also its maturation process, by targeting some of the proteins in the inflammasome.

In addition, they showed that IL-37 prevents pyroptosis—a form of inflammatory cell death which releases danger signals and encourages inflammation.

What does this mean for the treatment of inflammatory diseases?

The team believe that people living with inflammatory diseases could benefit from IL-37 as a therapeutic, to block the inflammation that drives the condition.

However, before IL-37 could potentially be used as a treatment, further research is required to ensure we fully understand its anti-inflammatory mechanisms and the effect they have on the body.

 “IL-37 is a promising candidate for clinical translation and our research helps to fill the existing knowledge gap, bringing us one step closer to our goal of advancing IL-37 towards clinical application,” said Dr Rudloff.

Collaborators
Royal College of Surgeons, Ireland; Monash University.

Funders
National Health and Medical Research Council (NHMRC), the National Heart Foundation Australia, Fielding Fellowship, Operational Infrastructure Support Program of the Victorian Government.

Research Groups leading this work