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Discovery of a new approach to the treatment of Lupus

Blockading the messenger substance Interleukin-6 prevents it from docking to the cell receptors and causing inflammation

(Vienna, 4 April 2016) Using an animal model, a research group at MedUni Vienna has discovered a potential new starting point for treating the autoimmune disease Systemic Lupus Erythematosus (SLE). Blockading the messenger substance Interleukin-6 prevents it from docking to the cell receptors and causing inflammation. The work has now been published in the journal "Experimental Dermatology".

The research group headed by Peter Birner (MedUni Vienna) and Lukas Kenner (MedUni Vienna, Vienna University of Veterinary Medicine and Ludwig Boltzmann Institute for Cancer Research) and including colleagues from Graz and from Germany and Japan has for the first time provided experimental proof that, in an animal model, a blockade of IL-6 brings about significant improvements in SLE.

In an earlier publication, the working group headed by Lukas Kenner (Pflegerl et al. 2009 in PNAS) was able to show that, in autoimmune diseases such as SLE, the production of Interleukin 6 (IL-6) from dermal keratinocytes plays a key role in the development and progression of the disease. The researchers used a transgenic murine model, in which the AP-1 transcription factor JunB was switched off in the epidermis. This showed that the expression of JunB inhibits the production of IL-6 in the skin. The loss of JunB in the skin then resulted in a very high systemic concentration of IL-6,, which leads to an SLE-like clinical picture.

The purpose of the present follow-up study was to use new drugs to block binding of IL-6 to the receptor (IL-6R alpha). Although we already have data evidencing the beneficial effect of an IL-6 blockade in rheumatoid arthritis, so far no data have been available for similar treatments for SLE. This data has now been provided, at least in an animal model. The mice that were treated displayed a significant improvement in skin lesions, even to the extent of complete remission.

Says lead author, Peter Birner of the Clinical Institute of Pathology: "The blockade of IL-6 receptor alpha could be a new treatment option for SLE patients with primary skin problems, and one with very few side-effects. This would be a great step forward in the treatment of this serious chronic disease."
And Lukas Kenner adds: "It is to be hoped that a significant improvement in symptoms can also be achieved in humans, as well as a significant prolongation of life by delaying invasive interventions."

Lupus Erythematosus
Systemic Lupus Erythematosus (SLE) is a common autoimmune disease, in which the human body forms antibodies against components of its own cells. This disease can involve a number of organs, the skin and kidneys being the most frequently affected.
So far the disease has essentially been treated by means of lifelong immunosuppression but this can involve significant side-effects.

Service: Experimental Dermatology
Birner P, Heider S, Petzelbauer P, Wolf P, Kornauth C, Kuroll M, Merkel O, Steiner G, Kishimoto T, Rose-John S, Soleiman A, Moriggl R, Kenner L: Interleukin-6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus. Exp Dermatol 2016 Apr;25(4):305-10. doi: 10.1111/exd.12934.

Five research clusters at MedUni Vienna
In total, five research clusters have been established at MedUni Vienna. In these clusters, MedUni Vienna is increasingly focusing on fundamental and clinical research. The research clusters include medical imaging, cancer research/oncology, cardiovascular medicine, medical neurosciences and immunology. This paper falls within the remit of the Cluster for Immunology.