Researchers Reveal a Promising Therapeutic Control Mechanism for Inflammation

Patricia Silva, PhD avatar

by Patricia Silva, PhD |

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painA study recently published in the journal Nature Immunology revealed a protein that is able to suppress inflammation in the body. The study is entitled “IL-37 requires the receptors IL-18Rα and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction.

Researchers led by Dr. Claudia Nold-Petry and Dr. Marcel Nold, both from Monash University and Ritchie Centre at MIMR-PHI Institute of Medical Research in Australia, have studied a protein called interleukin 37 (IL-37), which is a strong inhibitor of inflammation. The research team had previously discovered that IL-37 acts more broadly than other anti-inflammatory mediators in terms of regulation of the immune response and protection of the body from damage. Now, the team reveals the mechanism underlying the use of IL-37 as a molecular signal to control and regulate inflammation in the body.

“We all need inflammation to protect us from the harmful effects of bacteria, viruses or cancer. But in many diseases, there is too much inflammation; good examples are stroke, heart attack and auto immune diseases such as Crohn’s Disease or lupus,” said Dr. Nold in a news release, suggesting that inflammation can be seen as a double-edged sword.

In the particular case of lupus, also referred to as lupus systemic erythematosus (SLE), it corresponds to an autoimmune disease where the body’s own immune system overreacts resulting in an attack to healthy joints and organs, inflammation and pain. “Rampant inflammation is harmful and leads to tissue damage, resulting in all kinds of side effects like pain, fatigue and regrettably also organ failure and death” said Dr. Nold.

“IL-37 is extremely potent and effective in controlling inflammation, but to make it medically useful we needed to know how it works and what it does to cells,” said Dr. Nold-Petry.

The research team used super resolution microscopy to shed light on IL-37’s mechanism of action. The use of these advanced tools at Monash University allowed the visualization of single molecules of IL-37 and the respective receptors (namely IL-1R8 and IL-18Rα), demonstrating for the first time that IL-37 positions itself on the surface of target cells and that a tripartite complex is rapidly assembled (IL37 – IL-1R8 – IL-18Rα). The binding of IL-37 to these specific receptors on target cells induces a signaling cascade that results in a mitigation of several molecular pathways used by the body to mount an inflammatory response. Silencing the receptors IL-1R8 or IL-18Rα impaired the anti-inflammatory activity of IL-37.

“It’s important to note that this research is very early stage, but if we build on our discoveries and develop them further, it will be possible to deliver substantial and meaningful benefits to patients suffering from lots of diseases, be they acute or chronic, in a newborn baby or a centenarian” noted Dr. Nold.

“Now we have deciphered these mechanisms we can pursue the medical potential of IL-37. This can be done by mimicking its effects when there is too much inflammation, or by blocking it when there is too little, like in cancer,” concluded Dr. Nold-Petry.

The research team believes that these findings can potentially contribute to the development of new drugs to control inflammation in patients suffering from acute or chronic inflammatory diseases such as lupus.