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Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation

Permanent lenke
https://hdl.handle.net/10037/23763
DOI
https://doi.org/10.1016/j.bbi.2021.10.017
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article.pdf (2.220Mb)
Publisert versjon (PDF)
Dato
2021-11-07
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Szabo, Attila; O'Connell, Kevin Sean; Ueland, Thor; Sheikh, Mashhood Ahmed; Agartz, Ingrid; Andreou, Dimitrios; Aukrust, Pål; Boye, Birgitte; Bøen, Erlend; Drange, Ole Kristian; Elvsåshagen, Torbjørn; Engh, John; Hope, Sigrun; Høegh, Margrethe Collier; Joa, Inge; Johnsen, Erik; Kroken, Rune Andreas; Lagerberg, Trine Vik; Lekva, Tove; Malt, Ulrik Fredrik; Melle, Ingrid; Morken, Gunnar; Nærland, Terje; Steen, Vidar Martin; Sørensen, Kjetil; Wedervang-Resell, Kirsten; Weibell, Melissa Anne Elin Authen; Westlye, Lars Tjelta; Steen, Nils Eiel; Andreassen, Ole; Djurovic, Srdjan
Sammendrag
Background -Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients.

Methods - We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (n = 1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; n = 1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers.

Results - We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA, IL-18R1), and increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol types and the expression of inflammasome system elements in SMI.

Conclusions - Based on these results, we suggest a role for inflammasome activation/dysregulation in SMI. Our findings further the understanding of possible underlying inflammatory mechanisms and may expose important therapeutic targets in SMI.

Forlag
Elsevier
Sitering
Szabo A, O'Connell K, Ueland T, Sheikh MA, Agartz I, Andreou D, Aukrust P, Boye B, Bøen E, Drange OK, Elvsåshagen T, Engh J, Hope SH, Høegh MC, Joa I, Johnsen E, Kroken R, Lagerberg TV, Lekva T, Malt UF, Melle I, Morken G, Nærland T, Steen VM, Sørensen K, Wedervang-Resell K, Weibell MAE, Westlye LT, Steen NE, Andreassen OA, Djurovic S. Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation. Brain, behavior, and immunity. 2021;99:299-306
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  • Artikler, rapporter og annet (UB) [3245]
Copyright 2021 The Author(s)

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