Mechanism of skin inflammation triggered by interleukin-2

© Fraunhofer ITEM, created with BioRender.com
Interleukin-2 is used in different doses for cancer therapy or to treat inflammatory diseases, with skin rashes as a common side effect.

Under the EU project “imSAVAR” financed by the Innovative Medicines Initiative (IMI), experts from a number of countries and disciplines are working together to improve the prediction of undesirable effects of medicines. A particular focus is on treatments that affect the immune system, such as CAR-T cells, antibodies and interleukins.

Researchers at Fraunhofer ITEM have taken a closer look at treatment with interleukin-2 (IL-2) and the side effects that have occurred. IL-2 is used for treating inflammatory diseases and cancer. However, this treatment is often associated with skin rashes. To ascertain the causes of these side effects, the researchers investigated how IL-2 triggers immune responses in the skin and what role the IL-2 receptor plays in this.

After carrying out subcutaneous IL-2 injections in mice, the researchers observed that various immune cells were accumulating in the skin, including innate lymphoid cells (ILC2), which produce IL-4 and IL-13, and dermal γδ T cells, which produce IL-17. This caused a shift leading to type 2 and type 17 immune responses. While examining the significance of the IL-2 receptor, they found that its reduction on regulatory T cells in the skin aggravated the skin inflammation.

In summary, the results show that immune cells in the innate immune system are the main cause of the side effects of IL-2 treatment and underscore the significance of the receptor in this process.

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Katherina Sewald

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Dr. Katherina Sewald

Head of Department of Preclinical Pharmacology and In-vitro Toxicology

Phone +49 511 5350-323