Brain, behavior, and immunity · 2021
Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Szabo Attila, O'Connell Kevin S, Ueland Thor, Sheikh Mashhood A, Agartz Ingrid, Andreou Dimitrios, Aukrust Pål, Boye Birgitte, Bøen Erlend, Drange Ole Kristian, Elvsåshagen Torbjørn, Engh John Abel, Hope Sigrun, Collier Høegh Margrethe, Joa Inge, Johnsen Erik, Kroken Rune Andreas, Vik Lagerberg Trine, Lekva Tove, Malt Ulrik Fredrik, Melle Ingrid, Morken Gunnar, Nærland Terje, Steen Vidar Martin, Sørensen Kjetil, Wedervang-Resell Kirsten, Auten Weibell Melissa, Westlye Lars T, Steen Nils Eiel, Andreassen Ole, Djurovic Srdjan
Аннотация
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.
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.