05.10.2026
New drug candidate for asthma shows promise in a mouse model
Researchers at the Research Centre Borstel, Leibniz Lung Centre, have modified an endogenous anti-inflammatory messenger substance so that it remains active in the body for longer. In a mouse model, the new variant of interleukin-37 significantly reduced the typical symptoms of allergic asthma.
Asthma is characterised by chronic inflammation of the airways. Typical symptoms include shortness of breath, a tightness in the chest, coughing and a wheezing sound when breathing. Cytokines play an important role in the development and persistence of this inflammation. These are chemicals produced by the immune system that can either promote or inhibit inflammatory responses. For the immune system to function properly, inflammatory processes must be able to be activated rapidly. However, once the infection has been successfully fought off, they must also be brought to an end just as quickly in order to prevent damage to the body’s own tissues. In chronic inflammatory conditions such as asthma, this balance is disrupted. The inflammatory response persists and damages the airways, which in turn leads to the symptoms mentioned above.
A natural messenger in the body curbs inflammation
Whilst numerous pro-inflammatory cytokines have been studied and their mechanisms of action elucidated, considerably less is known about their natural antagonists. One such antagonist is interleukin-37 (IL-37). The Lung Immunology research group at the Research Centre Borstel, Leibniz Lung Centre, has been investigating this signaling molecule for more than ten years.
In 2015, the researchers showed that IL-37 can reduce allergic inflammation of the airways in mice. They also found lower levels of IL-37 in children with allergic asthma than in healthy children (1). “These findings raised the question of whether IL-37's natural anti-inflammatory mechanism could potentially be used as a basis for treatment,” says Dr Michael Wegmann, Head of the Lung Immunology research group at Research Center Borstel, Leibniz Lung Center.
In a further study, the team investigated in more detail how IL-37 exerts its effect. To do this, the substance binds to specific structures on or within cells. These structures are called receptors. Basically, they function as a kind of receiver for signals. The researchers were able to identify this previously unknown receptor and further demonstrate that IL-37 attenuates pro-inflammatory signals via this receptor. These include signals from the cytokines IL-1 and IL-33, which play a key role in the development of allergic inflammatory reactions in the airways (2). The research thus provides an explanation of how the body’s own anti-inflammatory signal can limit the excessive immune response in allergic asthma.
Contact
PD Dr. Michael Wegmann Leiter der Forschungsgruppe "Lungen-Immunologie" +49 4537 / 188-5830 
Improving the properties of IL-37
However, natural IL-37 has a limitation for potential medical use: it is broken down relatively quickly in the body and therefore does not remain active for long. Furthermore, IL-37 molecules can bind to one another. As a result, less IL-37 is available to perform its actual function. In collaboration with researchers from Australia, the Lung Immunology research group has therefore specifically modified the human molecule, which is also effective in mice. They developed an IL-37-Fc fusion protein with improved pharmacokinetic properties, ensuring that it remains available in the body and can exert its anti-inflammatory effect for longer. Crucially, unlike natural IL-37, it is suitable for pharmaceutical use.
Effective in an animal model
In the study, now published in the journal Allergy, the modified IL-37 was investigated in a mouse model of allergic asthma. The result: following local administration, the modified IL-37 reduced the key features of experimental asthma, particularly airway inflammation and breathing difficulties. At the same time, this effect was observed even at a significantly lower dose than that required for natural IL-37 (3). “This represents a major step forward in efforts to harness the anti-inflammatory effect of IL-37 for the treatment of patients with asthma. There is still a long way to go, but the results in the animal model are very encouraging,” explains first author Dr Lars Lunding from the Borstel research group.
Sources:
(1) 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):366-73. https://doi.org/10.1111/all.12566
(2) 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
(3) 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