Peripheral Interleukin-18 is negatively correlated with abnormal brain activity in patients with depression: a resting-state fMRI study

Du, Xiangdong; Zou, Siyun; Yue, Yan; Fang, Xiaojia; Wu, Yuxuan; Wu, Siqi; Wang, Haitao; Li, Zhe; Zhao, Xuechao; Yin, Ming; Ye, Gang; Sun, Hongyan; Gu, Xingfang; Zhang, Xiaobin; Miao, Zhigang; Jin, Jeff Wang; Wu, Hanjing Emily; Xu, Xingshun

doi:10.1186/s12888-022-04176-8

Cited by 10 publications

(6 citation statements)

References 48 publications

(52 reference statements)

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“…IL18 has pleiotropic functions. IL18 was increased and peripheral IL18 was negatively correlated with brain activity in depressed patients [ 9 , 56 ]. Moreover, the administration of IL18 into the amygdala, but not the hippocampus, led to severe depression-like behaviors [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Acute stress induces severe neural inflammation and overactivation of glucocorticoid signaling in interleukin-18-deficient mice

Yamanishi

Doe²,

Mukai³

et al. 2022

Transl Psychiatry

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Interleukin-18 (IL18) is an inflammatory cytokine that is related to psychiatric disorders such as depression and cognitive impairment. We previously found that IL18 deficiency may cause hippocampal impairment, resulting in depression-like behavioral changes. However, the potential role of IL18 in stressful conditions remains uncertain. In the present study, we examined the effect of IL18 on neural inflammation and stress tolerance during acute stress. Littermate Il18+/+ and Il18−/− mice were exposed to a single restraint stress for 6 h, and all assessments were performed 18 h after the mice were released from the restraint. In Il18−/− mice exposed to acute stress, the immobility times in both the forced swim test and tail suspension test were decreased, although no difference was observed in Il18+/+ mice. Il1β, Il6, and Tnfα expression levels in the hippocampus of stressed Il18−/− mice were significantly higher than those in the other groups. Moreover, the numbers of astrocytes and microglia, including those in the active form, were also increased compared with those in other groups. Regarding the molecular mechanism, the HSF5 and TTR genes were specifically expressed in stressed Il18−/− mice. As a potential treatment, intracerebral administration of IL18 to Il18−/− mice resulted in partial recovery of changes in behavioral assessments. Our results revealed that IL18-deficient mice were more sensitive and had a longer response to acute stress than that in normal mice. In addition, neural inflammation and augmentation of glucocorticoid signals caused by stress were more intense and remained longer in Il18−/− mice, resulting in behavioral changes. In conclusion, IL18 might be an indispensable factor that modulates the stress response and maintains balance between neural inflammation and glucocorticoid signaling.

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Section: Discussionmentioning

confidence: 99%

Acute stress induces severe neural inflammation and overactivation of glucocorticoid signaling in interleukin-18-deficient mice

Yamanishi

Doe²,

Mukai³

et al. 2022

Transl Psychiatry

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“…IL-18 is constitutively produced by cells of the immune system, but microglial cells, ependymal cells, and neurons also produce this cytokine. IL-18 can increase due to activation of the HPA axis and has been linked to brain disorders such as depression and cognitive impairment [ 93 , 94 ]. In addition, IL-18-deficient mice show abnormalities in stress response [ 92 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD

Valenza,

Facchinetti,

Torazza

et al. 2024

Transl Psychiatry

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Stress affects the brain and alters its neuroarchitecture and function; these changes can be severe and lead to psychiatric disorders. Recent evidence suggests that astrocytes and microglia play an essential role in the stress response by contributing to the maintenance of cerebral homeostasis. These cells respond rapidly to all stimuli that reach the brain, including stressors. Here, we used a recently validated rodent model of post-traumatic stress disorder in which rats can be categorized as resilient or vulnerable after acute inescapable footshock stress. We then investigated the functional, molecular, and morphological determinants of stress resilience and vulnerability in the prefrontal cortex, focusing on glial and neuronal cells. In addition, we examined the effects of a single subanesthetic dose of ketamine, a fast-acting antidepressant recently approved for the treatment of resistant depression and proposed for other stress-related psychiatric disorders. The present results suggest a prompt glial cell response and activation of the NF-κB pathway after acute stress, leading to an increase in specific cytokines such as IL-18 and TNF-α. This response persists in vulnerable individuals and is accompanied by a significant change in the levels of critical glial proteins such as S100B, CD11b, and CX43, brain trophic factors such as BDNF and FGF2, and proteins related to dendritic arborization and synaptic architecture such as MAP2 and PSD95. Administration of ketamine 24 h after the acute stress event rescued many of the changes observed in vulnerable rats, possibly contributing to support brain homeostasis. Overall, our results suggest that pivotal events, including reactive astrogliosis, changes in brain trophic factors, and neuronal damage are critical determinants of vulnerability to acute traumatic stress and confirm the therapeutic effect of acute ketamine against the development of stress-related psychiatric disorders.

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“… 20 Although, the biomarkers IL18 and IL1b have been previously demonstrated to exhibit associations with PD or stress‐related disorders, similar to the findings observed in our study. 31 …”

Section: Discussionmentioning

confidence: 99%

“…20 Although, the biomarkers IL18 and IL1b have been previously demonstrated to exhibit associations with PD or stressrelated disorders, similar to the findings observed in our study. 31 Cortisol is the most widely studied biomarker for PD, often measured in hair. 9 However, studies examining immunological biomarkers in relation to PD are limited.…”

Section: Main Findings and Interpretation Of The Findingsmentioning

confidence: 99%

Exploring the potential of stratum corneum biomarkers for assessing psychological distress in health care workers: An observational pilot study

Emal,

Tamminga,

Schaafsma

et al. 2024

Health Science Reports

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BackgroundsThe detection of biomarkers of a stress response in the stratum corneum (SC) could be used as objective assessment of early stress symptoms and monitoring of stress reduction interventions in health care workers (HCWs).AimThe aim of this study is to explore SC biomarkers of immune and hormonal response and skin barrier for assessment of psychological distress (PD) in HCWs.MethodsTwenty‐five female HCWs and 25 non‐HCWs participated. SC samples were collected using adhesive tapes at baseline and 3−5 days later (T1). We analyzed 24 biomarkers (immunological, vascular, hormones, and natural moisturizing factors). Stress symptoms were assessed using three scales of Copenhagen Psychosocial Questionnaire. The study involved: identifying SC biomarkers, correlating stress symptoms and biomarkers at baseline and T1, examining stress symptoms between the groups with a Mann‐Whitney test, comparing stress symptoms and biomarkers between groups using Ordinary Least Regression and investigating temporal variability of SC biomarkers at baseline and T1 using a Wilcoxon‐signed rank.ResultsFourteen SC biomarkers were identified. We found correlations between general stress and “IL18” (r = 0.55) physical stress and “IL1b” (r = 0.36) and cognitive stress and “MIP3a” (r = 0.38) at baseline and general stress and cortisol (r = −0.49), physical stress and cortisol (r = −0.60) and cortisone (r = −0.67) at T1. We found no differences in stress symptoms and biomarkers between the groups, except for “MIP3a” at baseline. Differences in the biomarker levels between two time points were found for “TARC,” “VEGFA,” “ILRA,” “IL1RA/IL1a,” “NMF,” and “DHEA.”ConclusionThe SC can be suitable biological material to assess biomarkers related to immune response, hormonal response, and skin barrier function. The SC biomarkers, showed strong, moderate and weak correlations with stress symptoms. Notably, these associations include cytokines of innate immunity and well‐known stress hormones, cortisol and cortisone.

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Peripheral Interleukin-18 is negatively correlated with abnormal brain activity in patients with depression: a resting-state fMRI study

Cited by 10 publications

References 48 publications

Acute stress induces severe neural inflammation and overactivation of glucocorticoid signaling in interleukin-18-deficient mice

Acute stress induces severe neural inflammation and overactivation of glucocorticoid signaling in interleukin-18-deficient mice

Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD

Exploring the potential of stratum corneum biomarkers for assessing psychological distress in health care workers: An observational pilot study

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