Hyperglycemia Is Associated with Psoriatic Inflammation in Both Humans and Mice

Abstract

Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself is correlated with hyperglycemia in humans and mice. In patients, the severity of psoriasis was correlated with high blood glucose levels, and treatment of psoriasis by phototherapy improved insulin secretion. Imiquimod-induced systemic and cutaneous inflammation in mice, with features of human psoriasis, also resulted in hyperglycemia. Although it should be determined if psoriasis-like cutaneous inflammation alone can induce hyperglycemia, imiquimod-treated mice showed impairment of insulin secretion without significant islet inflammation. Administration of anti-IL-17A monoclonal antibody improved hyperglycemia in patients with psoriasis and imiquimod-treated mice with psoriasiform features. These results suggest that hyperglycemia is highly associated with psoriasis, mainly through IL-17.

IL-17 May Be a Key Cytokine Linking Psoriasis and Hyperglycemia

“…Psoriasis is a multimorbid disease with significant patient impact, and effectively treating the condition-and its associated comorbidities-requires a good understanding of the immunopathological pathways underpinning this disease. Ikumi et al (2019) have provided intriguing data, suggesting how a cutaneous and systemic connection between psoriasis and diabetic states exists in both mice and humans and that IL-17 may play a contributory role.…”

“…Although the mechanisms behind these complex relationships have yet to be fully elucidated, it is currently known that psoriasis results from the interplay between genetic and environmental factors, leading to chronic dysregulated cutaneous and systemic inflammation centered around the IL-23/IL-17 T-cell axis (Hawkes et al, 2017). Ikumi et al (2019) bring us one step closer to piecing this puzzle together by providing compelling evidence for a link between psoriatic inflammation and hyperglycemia, via IL-17.…”

“…Severity of psoriasis correlates with hyperglycemia in humans and improves with antieIL-17A monoclonal antibody treatment Ikumi et al (2019) studied 39 patients with psoriasis and found a significant positive correlation between patients' Psoriasis Area Severity Index (PASI) score and their serum glycated hemoglobin (HbA1c) level, which reflects the average serum glucose level over the previous few months (Spearman r ¼ 0.582 [95% CI ¼ 0.3177e0.7623], P ¼ 0.0001). In addition to finding a correlation between the HbA1c level and total PASI score, there was also a correlation with the erythema component of the PASI score.…”

“…The second section of the paper by Ikumi et al (2019) details the use of an imiquimod (IMQ)-induced mouse model of cutaneous inflammation to explore the potential link between psoriasiform inflammation and glucose metabolism. The authors then attempted to tease out the underlying mechanisms for this inflammation by targeting the pathways involving IL-17.…”

“…The final stage of the work performed in the mouse model by Ikumi et al (2019) aimed to assess the effects of antieIL-17A mAb on hyperglycemia. This is because the IMQ mouse model mediates inflammation through IL-23/ IL-17 as mentioned previously (van der Fits et al, 2009); IL-17A blockade in humans improved hyperglycemia, and murine pancreatic islets express IL-17 receptors (Han et al, 2011).…”