Question: Psoriasis, an Interleukin-17A mediated chronic, auto-inflammatory disease is associated with various comorbidities such as cardiovascular or metabolic diseases. Meanwhile Psoriasis has been accepted as a new cardiovascular risk factor on its own, whereby a correlation between obese patients, the development of psoriasis and an exacerbation of symptoms is suspected. Thereupon, the straight-forward aim of this project was to investigate the impact of the Western diet (WD), a high-fat-diet, on dermal, systemic and vascular inflammation in a mouse model of Interleukin-17A driven psoriasis-like skin disease.
Methods: Four to six weeks old hetero- and homozygous CD11cCre-positive-IL-17Aind psoriatic mice (IL-17A overexpression in dendritic cells as model of moderate psoriasis) were fed with Western Diet vs Regular Diet (RD) over 16 weeks, to simulate the effects of fatty nutrition. After 16 weeks on a diet, the mice were euthanized and the organs liver, spleen, skin and Aorta as well as the epididymal and inguinal adipose tissue were examined more closely to investigate the strength of the different inflammations. Various methods such as flow cytometry, oxidative stress measurements, ELISA, q-PCR, histological examinations and an aortic relaxation measurement are performed.
Results: Especially the homozygous psoriatic mice which were fed with WD showed an increased neutrophil infiltration in the skin and exacerbating dermal inflammation compared to the homozygous mice on RD. Additionally, feeding WD to homozygous psoriatic mice led to higher counts of neutrophils and increased concentrations of the cytokine IL-17A in the blood in correlation with increasing severity of the psoriasis. Furthermore, the homozygous mice tended to have elevated GTP/ALT levels after eight weeks on diet, which indicates early liver damage. Moreover, homozygous psoriatic mice fed with WD tended to have a reduced relaxation ability on acetylcholine and seemed to be associated with an increased production of ROS/RNS. Summary: Overall, the Western Diet seems to be more than a cardiovascular risk factor on top and interact in several ways with dermal, vascular and liver inflammation which leads to more serious consequences. This has to be considered in patients with autoimmune diseases that are associated with cardiovascular disease. Further analysis will be carried out to improve the treatment options.
