DZL researchers at the ARCN site have modified a naturally occurring anti-inflammatory messenger molecule to prolong its activity in the body. In a mouse model, the modified version of interleukin-37 significantly reduced airway inflammation and other features of allergic asthma.
Asthma is a chronic inflammatory disease of the airways. Immune messenger molecules known as cytokines play an important role in the development and persistence of this inflammation. While some cytokines promote inflammatory responses, others help to suppress them. In asthma, this balance is disrupted, allowing inflammation to persist and damage the airways.
Interleukin-37 (IL-37) is a natural antagonist of pro-inflammatory signals. Researchers at the LungenClinic Großhansdorf, part of the DZL's ARCN site, have been investigating how this naturally occurring messenger molecule influences inflammatory responses for more than ten years. Previous studies showed that IL-37 can reduce allergic airway inflammation in mice. In addition, lower levels of IL-37 were found in children with allergic asthma than in healthy children.
Natural IL-37 has limitations that complicate its potential medical use: it is broken down relatively quickly in the body and therefore remains active for only a short time. In addition, IL-37 molecules can bind to one another, reducing the amount available to exert their intended effects. To overcome these limitations, the research team worked with scientists in Australia to develop a modified version of human IL-37. The resulting IL-37-Fc fusion protein has improved pharmacokinetic properties. It remains available in the body for longer and can exert its anti-inflammatory effects over an extended period. Compared with the natural molecule, the modified version is also better suited for potential pharmaceutical development.
In the study, recently published in the journal Allergy, the research team investigated the efficacy of the modified IL-37 in a mouse model of allergic asthma. Following local administration, key features of the disease were reduced, particularly airway inflammation and breathing difficulties. The effects were observed at a substantially lower dose than that required for natural IL-37.
These findings represent an important step towards harnessing the anti-inflammatory properties of this naturally occurring messenger molecule for a potential asthma treatment. However, further research is needed before it can be used in patients. The results from this animal model provide a promising basis for future investigations.
Original publications:
Lunding L, Webering S, Vock C, Schröder A, Raedler D, Schaub B, Fehrenbach H, Wegmann M. IL-37 requires IL-18Rα and SIGIRR/IL-1R8 to diminish allergic airway inflammation in mice. Allergy. 2015 Apr;70(4):366–373. https://doi.org/10.1111/all.12566
Schröder A, Lunding LP, Zissler UM, Vock C, Webering S, Ehlers JC, Orinska Z, Chaker A, Schmidt-Weber CB, Lang NJ, Schiller HB, Mall MA, Fehrenbach H, Dinarello CA, Wegmann M. IL-37 regulates allergic inflammation by counterbalancing pro-inflammatory IL-1 and IL-33. Allergy. 2022 Mar;77(3):856–869. https://doi.org/10.1111/all.15072
Lunding LP, Nold MF, Nold-Petry CA, Wegmann M. Local Delivery of a Bio-Engineered IL-37 Fc-Fusion Ameliorates Experimental Allergic Asthma in Mice. Allergy. 2026 Sep 3. doi: 10.1111/all.70509. https://doi.org/10.1111/all.70509
