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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Aug 9

PMID 34367160

Citations 19

Authors

Efterpi Zafiriou

Athina I Daponte

Vasileios Siokas

Christina Tsigalou

Efthymios Dardiotis

Dimitrios P Bogdanos

Affiliations

Soon will be listed here.

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.

Citing Articles

The Role of Metabolic Syndrome in Psoriasis Treatment Response: A One-Year Comparative Analysis of PASI Progression.

Mustata M, Ionescu M, Radu L, Neagoe C, Ahritculesei R, Cimpeanu R Diagnostics (Basel). 2025; 14(24.

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Metabolic syndrome and psoriatic arthritis: the role of weight loss as a disease-modifying therapy.

Williams J, Hum R, Rogers K, Maglio C, Alam U, Zhao S Ther Adv Musculoskelet Dis. 2024; 16:1759720X241271886.

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Altered serum interleukin-17A and interleukin-23A levels may be associated with the pathophysiology and development of generalized anxiety disorder.

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Analysis of Clinical and Genetic Factors of Obesity and Psoriasis Concomitance-The Influence of Body Mass Composition, Prevalence of Mood Disorders, Environmental Factors and Gene Polymorphisms (rs9939609, rs1558902).

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PMID: 38540130 PMC: 10968415. DOI: 10.3390/biomedicines12030517.

References

Griffiths C, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A . Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015; 386(9993):541-51. DOI: 10.1016/S0140-6736(15)60125-8. View

Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H . Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med. 2002; 8(5):500-8. DOI: 10.1038/nm0502-500. View

Mease P, van der Heijde D, Ritchlin C, Okada M, Cuchacovich R, Shuler C . Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled.... Ann Rheum Dis. 2016; 76(1):79-87. PMC: 5264219. DOI: 10.1136/annrheumdis-2016-209709. View

Chauvet-Gelinier J, Roussot A, Cottenet J, Brindisi M, Petit J, Bonin B . Depression and obesity, data from a national administrative database study: Geographic evidence for an epidemiological overlap. PLoS One. 2019; 14(1):e0210507. PMC: 6324832. DOI: 10.1371/journal.pone.0210507. View

Huang M, Su S, Goldberg J, Miller A, Levantsevych O, Shallenberger L . Longitudinal association of inflammation with depressive symptoms: A 7-year cross-lagged twin difference study. Brain Behav Immun. 2018; 75:200-207. PMC: 6279462. DOI: 10.1016/j.bbi.2018.10.007. View

Genovese M, Mysler E, Tomita T, Papp K, Salvarani C, Schwartzman S . Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. Rheumatology (Oxford). 2020; 59(12):3834-3844. PMC: 7733711. DOI: 10.1093/rheumatology/keaa189. View

Beurel E, Lowell J, Jope R . Distinct characteristics of hippocampal pathogenic T17 cells in a mouse model of depression. Brain Behav Immun. 2018; 73:180-191. PMC: 6287768. DOI: 10.1016/j.bbi.2018.04.012. View

Sukoff Rizzo S, Neal S, Hughes Z, Beyna M, Rosenzweig-Lipson S, Moss S . Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes. Transl Psychiatry. 2012; 2:e199. PMC: 3565187. DOI: 10.1038/tp.2012.120. View

Raison C, Rutherford R, Woolwine B, Shuo C, Schettler P, Drake D . A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2012; 70(1):31-41. PMC: 4015348. DOI: 10.1001/2013.jamapsychiatry.4. View

10.

Sakkas L, Bogdanos D . Are psoriasis and psoriatic arthritis the same disease? The IL-23/IL-17 axis data. Autoimmun Rev. 2016; 16(1):10-15. DOI: 10.1016/j.autrev.2016.09.015. View

11.

Kumar P, Chan Wei Shih D, Lim A, Paleja B, Ling S, Li Yun L . Pro-inflammatory, IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy. JCI Insight. 2019; 5. PMC: 6538358. DOI: 10.1172/jci.insight.126337. View

12.

Nadeem A, Ahmad S, Al-Harbi N, Fardan A, El-Sherbeeny A, Ibrahim K . IL-17A causes depression-like symptoms via NFκB and p38MAPK signaling pathways in mice: Implications for psoriasis associated depression. Cytokine. 2017; 97:14-24. DOI: 10.1016/j.cyto.2017.05.018. View

13.

Beurel E, Lowell J . Th17 cells in depression. Brain Behav Immun. 2017; 69:28-34. PMC: 5797502. DOI: 10.1016/j.bbi.2017.08.001. View

14.

Davami M, Baharlou R, Vasmehjani A, Ghanizadeh A, Keshtkar M, Dezhkam I . Elevated IL-17 and TGF-β Serum Levels: A Positive Correlation between T-helper 17 Cell-Related Pro-Inflammatory Responses with Major Depressive Disorder. Basic Clin Neurosci. 2016; 7(2):137-42. PMC: 4892318. DOI: 10.15412/J.BCN.03070207. View

15.

Liu Y, Zhang C, Li B, Yu C, Bai X, Xiao C . A novel role of IL-17A in contributing to the impaired suppressive function of Tregs in psoriasis. J Dermatol Sci. 2020; 101(2):84-92. DOI: 10.1016/j.jdermsci.2020.09.002. View

16.

Paroutoglou K, Papadavid E, Christodoulatos G, Dalamaga M . Deciphering the Association Between Psoriasis and Obesity: Current Evidence and Treatment Considerations. Curr Obes Rep. 2020; 9(3):165-178. DOI: 10.1007/s13679-020-00380-3. View

17.

Cai Y, Shen X, Ding C, Qi C, Li K, Li X . Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation. Immunity. 2011; 35(4):596-610. PMC: 3205267. DOI: 10.1016/j.immuni.2011.08.001. View

18.

Patel D, Lee D, Kolbinger F, Antoni C . Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis. 2012; 72 Suppl 2:ii116-23. DOI: 10.1136/annrheumdis-2012-202371. View

19.

McIntyre R, Subramaniapillai M, Lee Y, Pan Z, Carmona N, Shekotikhina M . Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019; 76(8):783-790. PMC: 6506894. DOI: 10.1001/jamapsychiatry.2019.0779. View

20.

Colasanto M, Madigan S, Korczak D . Depression and inflammation among children and adolescents: A meta-analysis. J Affect Disord. 2020; 277:940-948. DOI: 10.1016/j.jad.2020.09.025. View