Depression and Obesity in Patients With Psoriasis and Psoriatic Arthritis: Is IL-17-Mediated Immune Dysregulation the Connecting Link?

Abstract

Patients with psoriasis are frequently obese and experience anxiety or suffer from depressive disorders. The immunopathogenesis of psoriasis and indeed psoriatic arthritis is largely based on the pivotal role of IL-17/IL-23 axis, to an extent that currently monoclonal antibodies selectively inhibiting IL-17 or IL-23 are routinely used for the treatment of psoriatic diseases. Emerging data, demonstrating a decisive role for IL-17 and IL-17 producing cell subsets, such as Th17 in the induction and progression of obesity and depression has led authors to suggest that psoriatic disease, obesity and anxiety/depression may indeed be interconnected manifestation of a state of immunedysregulation, the linked being IL-17 and its related cells. We discuss this hypothetical link in depth taking into account the beneficial effects anti-IL17 and anti-IL-17 receptor inhibitors in treating psoriatic disease and the on-going debate as to whether these biologics may exert a direct or indirect effect in ameliorating concomitant obesity and depressive disorders, which are frequently noted in the same patient.

Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Considering that in patients with ME/CFS, the intestinal microbiome has an increased ability to produce lactate [ 45 ], and that tissue hypoperfusion due to anomalies of peripheral blood flow auto-regulation has been proposed as a possible pathogenetic mechanism of ME/CFS [ 22 ], the relationship between energy metabolism and Th17 polarization may merit further scrutiny. Finally, it has been recently suggested that IL-17A may play a role in depression associated with psoriasis and obesity [ 46 ]. The present data suggest that it might be worthwhile to see if a relationship exists between IL-17A serum levels and ME/CFS-associated depression.…”

Downregulated NPAS4 in multiple brain regions is associated with Major Depressive Disorder

“…Enrichment of differentially expressed genes yielded 18 pathways (padj<0.05) related to inflammation, such as the IL17 signaling pathway, Rheumatoid arthritis, NF-kappa B signaling pathway. It has been previously suggested that IL-17A induces depressive behavior in mice (Kim et al, 2021; Nadeem et al, 2017), but studies for humans (Saraykar et al, 2017; Tsuboi et al, 2018; Zafiriou et al, 2021) have contradicting conclusions. Lui et al (2011) showed that higher serum levels of IL-17 are positively correlated with the severity of anxiety in patients with rheumatoid arthritis.…”

The Role of IL-17 Cytokines in Psoriasis

“…Several studies with conflicting evidence suggest IL-17 may be the immunologic link between psoriasis and depression. 33 Elevated IL-17 levels are hypothesized to mediate depressive disorders through downstream activation of microglia and neuroinflammation with chemokines, cytokines, and neuroinflammatory mediators. 33 The upregulation of IL-17 gene expression and increased serum levels in patients with major depressive disorders compared to healthy controls support IL-17 involvement in the disease process.…”

“… 33 Elevated IL-17 levels are hypothesized to mediate depressive disorders through downstream activation of microglia and neuroinflammation with chemokines, cytokines, and neuroinflammatory mediators. 33 The upregulation of IL-17 gene expression and increased serum levels in patients with major depressive disorders compared to healthy controls support IL-17 involvement in the disease process. 34–37 In addition, mouse models of depressive brains demonstrated increased percentages of Th17 cells and increased levels of IL-17 interleukins.…”

“…In addition, IL-17 may mediate the feed-forward inflammatory cycle associated with obesity. 33 Adipocytes and macrophages in visceral adipose tissue exacerbate the inflammatory state of psoriasis by promoting several pro-inflammatory cytokines, including IL-6, which mediates Th17 commitment by naïve T cells. 41 , 42 IL-17 activates the positive feedback process by stimulating the production of IL-6.…”