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IL-33 in Mental Disorders.

ABSTRACT: Mental disorders are common in the general population; every year about 25% of the total European population is affected by a mental condition. The prevalence of psychiatric disorders might be underestimated. Emerging evidence highlights the role of immune response as a key factor in MDs. Immunological biomarkers seem to be related to illness progression and to treatment effectiveness; several studies suggest strong associations among IL-6, TNFa, S100b, IL 1b, and PCR with affective or schizophrenic disorders. The purpose of this review is to examine and to understand the possible link between mental disorders and interleukin 33 to clarify the role of this axis in the immune system. We found 13 research papers that evaluated interleukin 33 or interleukin 31 levels in subjects affected by mental disorders. Eight studies investigated cytokines in affective disorders. Three studies measured levels of IL-33 in schizophrenia and two studies focused on patients affected by autism spectrum disorders. Alterations in brain structure and neurodevelopmental outcome are affected by multiple levels of organization. Disorders of the autoimmune response, and of the IL-33/31 axis, may therefore be one of the factors involved in this process. These results support the evidence that alarmins, particularly the IL-33/31 axis, need more consideration among researchers and practitioners.

SUBMITTER: Pandolfo G

PROVIDER: S-EPMC8066291 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:We tested the hypothesis that the expression of IL-33 in MS is dynamic and is likely to reflect the clinical and radiological changes during the course of RRMS. METHODS:MS with either clinical or radiological relapses were recruited for the study and followed for one year. IL-33 and a panel of genes was measured by q PCR and flow cytometry at different time points. RESULTS:Among 22 RRMS patients, 4 patients showed highest levels of IL-33 at the time they were recruited to the study (Month 0); in 14 patients highest levels of IL-33 were seen between 6-11 months after relapse and in 4 patients maximal levels of IL-33 were seen 12 months after relapse. A similar pattern of IL-33 kinetics was seen when IL-33 was measured by flow cytometry in an additional cohort of 12 patients. The timing of the improvement clinically did not correlate with IL-33 expression with highest expression levels either preceding or following clinical recovery. From our whole genome RNA-sequencing data we found a strong correlation between expression levels of IL-33 and a ~2000 mRNA genes. However, none of these genes encoded proteins involved in either innate or adaptive immunity. Rather, many of the genes that correlated highly with IL-33 encoded to proteins involved in DNA repair or mitochondrial function and mRNA splicing pathways. INTERPRETATION:Given the neuro-reparative and remodeling functions attributed to IL-33, it is likely that some of the novel genes we have uncovered may be involved in repair and recovery of the CNS in MS.

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IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut.

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