Brain, Behavior, and Immunity最新文献

{"title":"Primary sensory neuron-derived miR-let-7b underlies stress-elicited psoriasis","authors":"Huan Yang ,&nbsp;Yun-Yun Wang ,&nbsp;Weiqi Chang ,&nbsp;Mengying Zhai ,&nbsp;Wan-Jie Du ,&nbsp;Wencheng Jiang ,&nbsp;Yan-Wei Xiang ,&nbsp;Guoyou Qin ,&nbsp;Jin Yu ,&nbsp;Ye Gong ,&nbsp;Qingjian Han","doi":"10.1016/j.bbi.2024.11.005","DOIUrl":"10.1016/j.bbi.2024.11.005","url":null,"abstract":"<div><div>Psoriasis, a chronic autoimmune skin condition with significant global morbidity, badly impairs patients’ quality of life. Stress has been identified as a prominent trigger for psoriasis, and effectively management of stress can ameliorate its pathological manifestations. However, the precise mechanisms by which stress influences psoriasis remain elusive. In this study, we found that mice subjected to chronic social defeat stress (CSDS) exhibit severer imiquimod (IMQ)-induced psoriasis with increased epidermal scaling, epidermal hyperplasia, number of epidermal ridges, itch, and skin inflammation than control mice. Mechanistic study reveals that CSDS leads to an elevated release of miR-let-7b, an endogenous ligand of Toll-like receptor 7 (TLR7), from the peripheral terminal of dorsal root ganglia (DRG) neurons into the skin. This process can stimulate skin-resident macrophages to release cytokines (such as IL-6 and TNF-a) and chemokines (such as MCP-1), subsequently promoting the recruitment of additional macrophages into the skin. Notably, the specific blockade of miR-let-7b in DRG neurons effectively relieve stress-induced exacerbations of psoriasis. Furthermore, intradermal injection of synthetic miR-let-7b can induce a psoriasis-like phenotype in wildtype mice, a phenomenon that can be countered by the application of a TLR7 antagonist. Additionally, microfluidic chamber coculture assays demonstrated that miR-let-7b released by DRG neurons activates macrophages via TLR7 expressed on these immune cells. Totally, this study found that stress-induced upregulation and release of miR-let-7b from DRG neurons stimulates macrophages to secrete more inflammatory cytokines and chemokines, thereby exacerbating skin inflammation and the psoriatic phenotype. These findings provide a potential therapeutic strategy targeting the miR-let-7b/TLR7 pathway to alleviate stress-induced exacerbation of psoriasis.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 997-1010"},"PeriodicalIF":8.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific associations between maternal prenatal inflammation and offspring cortical morphology in youth: A harmonised study across four birth cohorts","authors":"Anni Niskanen ,&nbsp;Aaron Barron ,&nbsp;Hatim Azaryah ,&nbsp;Martta Kerkelä ,&nbsp;Elmo Pulli ,&nbsp;Jetro J. Tuulari ,&nbsp;Minna Lukkarinen ,&nbsp;Linnea Karlsson ,&nbsp;Ryan L. Muetzel ,&nbsp;Cristina Campoy ,&nbsp;Andrés Catena ,&nbsp;Henning Tiemeier ,&nbsp;Golam M. Khandaker ,&nbsp;Hasse Karlsson ,&nbsp;Juha Veijola ,&nbsp;Lassi Björnholm","doi":"10.1016/j.bbi.2024.11.010","DOIUrl":"10.1016/j.bbi.2024.11.010","url":null,"abstract":"<div><div>Maternal immune activation (MIA) during pregnancy is implicated in offspring psychiatric disorders. However, it is unknown to what extent MIA affects neurodevelopment, particularly cerebrocortical anatomy, in the general population, and whether effects differ by sex. The current study used vertex-wise statistics to examine the association between maternal prenatal CRP, an archetypal systemic inflammatory marker, and offspring cortical thickness, surface area, and volume, in 2635 mother–child dyads (5.4–26.5 years) from three population-based cohorts, and one clinical cohort enriched for presence of inflammation markers.</div><div>Maternal CRP within a normal physiological range (&lt;10 mg/L) exhibited sex-specific quadratic associations with cortical morphological measures in 2 regions in males and 1 region in females at childhood. Elevated (&gt;10 mg/L) CRP was associated with regional cortical morphology in females and in a pooled sample of sexes. Overall, MIA is associated with cortical development in a regional and sex-specific manner in studies spanning childhood to adulthood.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 1081-1090"},"PeriodicalIF":8.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis.","authors":"Matthew Jy Kang, Jasleen Grewal, Dhamidhu Eratne, Charles Malpas, Wei-Hsuan Chiu, Kasper Katisko, Eino Solje, Alexander F Santillo, Philip B Mitchell, Malcolm Hopwood, Dennis Velakoulis","doi":"10.1016/j.bbi.2024.11.001","DOIUrl":"10.1016/j.bbi.2024.11.001","url":null,"abstract":"<p><p>Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal injury measurable in cerebrospinal fluid (CSF) and blood. Despite their potential as diagnostic tests for neurodegenerative disorders, it is unclear how they behave in mood and anxiety disorders. We conducted a systematic review and meta-analysis to investigate whether NfL and GFAP concentrations were altered in adults with mood and anxiety disorders compared to healthy controls. We searched PubMed, Web of Science, PsycINFO, MEDLINE and Embase through August 20, 2024, and assessed relevant studies and their risk of bias. The primary outcome was the standardised mean difference (SMD) and 95 % confidence interval (95 % CI) of NfL and GFAP concentrations. Twenty-nine studies comprising 2,962 individuals (927majordepression,804bipolardisorder,and1,231controls). When we compared individuals with major depression and healthy controls, there was no difference in NfL nor GFAP levels. In individuals with bipolar disorder, NfL was significantly elevated compared to controls (SMD = 0.53; 95 % CI: 0.20, 0.85; p = 0.005). Only one study reported on NfL levels anxiety disorders. Our study informs clinicians about how to interpret these emerging biomarkers in determining whether a person's symptoms are caused by a neurodegenerative or mood disorder. The mild elevation of NfL in bipolar disorder may suggest underlying neuroaxonal injury, warranting further research into its clinical and prognostic significance.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":"1091-1102"},"PeriodicalIF":8.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting the early warning signs of neonatal brain injury","authors":"Stella Liong","doi":"10.1016/j.bbi.2024.11.009","DOIUrl":"10.1016/j.bbi.2024.11.009","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 948-949"},"PeriodicalIF":8.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-derived cyclooxygenase-2 fuels hypothalamic inflammation","authors":"Xiaolin Li ,&nbsp;Xinxia Zhu ,&nbsp;Parham Diba ,&nbsp;Xuan Shi ,&nbsp;Frank Vrieling ,&nbsp;Fleur A.C. Jansen ,&nbsp;Michiel G.J. Balvers ,&nbsp;Ian de Bus ,&nbsp;Peter R. Levasseur ,&nbsp;Ariana Sattler ,&nbsp;Paige C. Arneson-Wissink ,&nbsp;Mieke Poland ,&nbsp;Renger F. Witkamp ,&nbsp;Klaske van Norren ,&nbsp;Daniel L. Marks","doi":"10.1016/j.bbi.2024.11.002","DOIUrl":"10.1016/j.bbi.2024.11.002","url":null,"abstract":"<div><div>Hypothalamic inflammation often coincides with cancer and cachexia-anorexia. Prior work established the significance of tumor-derived inflammatory factors in triggering hypothalamic inflammation, yet the precise mechanisms remained elusive. Here, we demonstrate that prostaglandin E2 (PGE2), produced in the tumor via cyclooxygenase-2 (COX-2), plays a pivotal role in this context. PGE2 itself directly exerts pro-inflammatory effects on the hypothalamus through the EP4 receptor, while also augmenting hypothalamic inflammation via NF-κB pathways in the presence of host gut-derived pathogen-associated molecular patterns (PAMPs). In tumor-bearing mice, we confirm this synergistic interaction between tumor-derived COX-2/PGE2 and host-derived lipopolysaccharide (LPS) in amplifying hypothalamic inflammation. Supporting this mechanism we find that the tumor-specific knockout of COX-2 attenuates hypothalamic inflammation and improves survival in mice. Together, these findings highlight the mechanisms of tumor-associated COX-2 in fuelling hypothalamic inflammation. They also emphasize the potential of tumor-specific COX-2 inhibition and targeting gut permeability as a novel therapeutic strategy for improving clinical outcomes in cancer patients.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 886-902"},"PeriodicalIF":8.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute exercise boosts NAD+ metabolism of human peripheral blood mononuclear cells","authors":"David Walzik ,&nbsp;Niklas Joisten ,&nbsp;Alexander Schenk ,&nbsp;Sina Trebing ,&nbsp;Kirill Schaaf ,&nbsp;Alan J Metcalfe ,&nbsp;Polyxeni Spiliopoulou ,&nbsp;Johanna Hiefner ,&nbsp;Adrian McCann ,&nbsp;Carsten Watzl ,&nbsp;Per Magne Ueland ,&nbsp;Sebastian Gehlert ,&nbsp;Anna Worthmann ,&nbsp;Charles Brenner ,&nbsp;Philipp Zimmer","doi":"10.1016/j.bbi.2024.11.004","DOIUrl":"10.1016/j.bbi.2024.11.004","url":null,"abstract":"<div><div>Nicotinamide adenine dinucleotide (NAD⁺) coenzymes are the central electron carriers in biological energy metabolism. Low NAD⁺ levels are proposed as a hallmark of ageing and several diseases, which has given rise to therapeutic strategies that aim to tackle these conditions by boosting NAD⁺ levels. As a lifestyle factor with preventive and therapeutic effects, exercise increases NAD⁺ levels across various tissues, but so far human trials are mostly focused on skeletal muscle. Given that immune cells are mobilized and redistributed in response to acute exercise, we conducted two complementary trials to test the hypothesis that a single exercise session alters NAD⁺ metabolism of peripheral blood mononuclear cells (PBMCs). In a randomized crossover trial (DRKS00017686) with 24 young adults (12 female) we show that acute exercise increases gene expression and protein abundance of several key NAD⁺ metabolism enzymes with high conformity between high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). In a longitudinal exercise trial (DRKS00029105) with 12 young adults (6 female) we confirm these results and reveal that – similar to skeletal muscle – NAD⁺ salvage is pivotal for PBMCs in response to exercise. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD⁺ salvage pathway, displayed a pronounced increase in gene expression during exercise, which was accompanied by elevated intracellular NAD⁺ levels and reduced serum levels of the NAD⁺ precursor nicotinamide. These results demonstrate that acute exercise triggers NAD⁺ biosynthesis of human PBMCs with potential implications for immunometabolism, immune effector function, and immunological exercise adaptions.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 1011-1023"},"PeriodicalIF":8.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claudin-5 and occludin levels in patients with psychiatric disorders − A systematic review","authors":"Zinovia Maridaki ,&nbsp;Georgios Syrros ,&nbsp;Stella Gianna Delichatsiou ,&nbsp;Jerry Warsh ,&nbsp;Gerasimos N. Konstantinou","doi":"10.1016/j.bbi.2024.11.006","DOIUrl":"10.1016/j.bbi.2024.11.006","url":null,"abstract":"<div><h3>Background</h3><div>Recent research has underscored the critical role of blood–brain barrier (BBB) integrity in psychiatric disorders, highlighting disruptions in tight junction (TJ) proteins, specifically claudin-5 and occludin. These proteins are pivotal in maintaining the BBB’s selective permeability, which is essential for<!--> <!-->brain homeostasis. Altered levels of the TJ proteins have been observed in various psychiatric conditions, suggesting potential as biomarkers for the pathophysiology of these disorders. This systematic review synthesizes existing research on the alterations of claudin-5 and occludin levels in the serum of individuals with psychiatric disorders, evaluating their correlation with BBB dysfunction and psychiatric pathophysiology.</div></div><div><h3>Methods</h3><div>In adherence to the PRISMA guidelines, a comprehensive search strategy was employed, utilizing databases such as PubMed, Google Scholar, Web of Science, and Scopus. The review encompassed studies published between 2000 and 2024 that measured serum claudin-5 and occludin levels of psychiatric patients. Thorough data extraction and synthesis were conducted.</div></div><div><h3>Results</h3><div>Seventeen studies met the inclusion criteria. Key findings include indications for increased claudin-5 levels in Schizophrenia, Bipolar Disorder, Depression, and Specific learning disorder, and increased occludin levels in ADHD and Autism Spectrum Disorder patients. No significant differences were found in studies of patients with Alcohol Use and Insomnia Disorder.</div></div><div><h3>Conclusions</h3><div>The review underscores the potential association between altered serum levels of claudin-5 and occludin and psychiatric disorders, supporting their utility as biomarkers for BBB integrity and psychiatric pathophysiology. Further research is essential to elucidate the mechanisms linking TJ protein alterations with pathophysiology and, potentially, neuroprogression in psychiatric disorders, which could lead to novel diagnostic and therapeutic strategies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 865-875"},"PeriodicalIF":8.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast-derived IL-33 exacerbates orofacial neuropathic pain via the activation of TRPA1 in trigeminal ganglion neurons","authors":"Yousuke Ikehata ,&nbsp;Eri Oshima ,&nbsp;Yoshinori Hayashi ,&nbsp;Yukinori Tanaka ,&nbsp;Hitoshi Sato ,&nbsp;Suzuro Hitomi ,&nbsp;Miho Shiratori-Hayashi ,&nbsp;Kentaro Urata ,&nbsp;Yuki Kimura ,&nbsp;Ikuko Shibuta ,&nbsp;Seigo Ohba ,&nbsp;Koichi Iwata ,&nbsp;Kentaro Mizuta ,&nbsp;Tatsuo Shirota ,&nbsp;Masamichi Shinoda","doi":"10.1016/j.bbi.2024.11.003","DOIUrl":"10.1016/j.bbi.2024.11.003","url":null,"abstract":"<div><div>Damage to the peripheral nerves of trigeminal ganglion (TG) neurons leads to intractable orofacial neuropathic pain through the induction of neuroinflammation. However, the details of this process are not yet fully understood. Here, we found that fibroblast-derived interleukin (IL)-33 was required for the development of mechanical allodynia in whisker pad skin following infraorbital nerve injury (IONI). The amount of IL-33 in the TG increased after IONI when the mice exhibited mechanical allodynia. Neutralization of IL-33 in the TG inhibited the development of IONI-induced mechanical allodynia. Conversely, intra-TG administration of recombinant human IL-33 (rhIL-33) elicited mechanical allodynia in naïve mice. IL-33 and its receptor were exclusively expressed in fibroblasts and neurons, respectively, in the TG. Fibroblast ablation caused the loss of IL-33 in the TG and delayed the development of mechanical allodynia after IONI. rhIL-33 elicited an increase in intracellular Ca²⁺ concentration and subsequent enhancement of Ca²⁺ influx via transient receptor potential ankyrin 1 (TRPA1) in primary cultured TG neurons. Additionally, rhIL-33 facilitated membrane translocation of TRPA1 in the TG. Mechanical allodynia caused by intra-TG administration of rhIL-33 was significantly inhibited by pharmacological blockade or gene silencing of TRPA1 in the TG. Inhibition of protein kinase A abrogated TRPA1 membrane translocation and delayed mechanical allodynia after IONI. Substance P stimulation caused upregulation of IL-33 expression in primary cultured fibroblasts. Preemptive administration of a neurokinin-1 receptor antagonist in the TG attenuated mechanical allodynia and IL-33 expression following IONI. Taken together, these results indicate that fibroblast-derived IL-33 exacerbates TG neuronal excitability via suppression of tumorigenicity 2 (ST2)-TRPA1 signaling, ultimately leading to orofacial neuropathic pain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 982-996"},"PeriodicalIF":8.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and long-term effects of COVID-19 on brain and mental health: A narrative review","authors":"J. Douglas Bremner ,&nbsp;Scott J. Russo ,&nbsp;Richard Gallagher ,&nbsp;Naomi M. Simon","doi":"10.1016/j.bbi.2024.11.007","DOIUrl":"10.1016/j.bbi.2024.11.007","url":null,"abstract":"<div><h3>Background</h3><div>COVID infection has been associated with long term sequalae (Long COVID) which include neurological and behavioral effects in thousands of patients, but the etiology and scope of symptoms is not well understood. This paper reviews long term sequelae of COVID on brain and mental health in patients with the Long COVID syndrome.</div></div><div><h3>Methods</h3><div>This was a literature review which queried databases for Pubmed, Psychinfo, and Medline for the following topics for January 1, 2020-July 15, 2023: Long COVID, PASC, brain, brain imaging, neurological, neurobiology, mental health, anxiety, depression.</div></div><div><h3>Results</h3><div>Tens of thousands of patients have developed Long COVID, with the most common neurobehavioral symptoms anosmia (loss of smell) and fatigue. Anxiety and mood disorders are elevated and seen in about 25% of Long COVID patients. Neuropsychological testing studies show a correlation between symptom severity and cognitive dysfunction, while brain imaging studies show global decreases in gray matter and alterations in olfactory and other brain areas.</div></div><div><h3>Conclusions</h3><div>Studies to date show an increase in neurobehavioral disturbances in patients with Long COVID. Future research is needed to determine mechanisms.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 928-945"},"PeriodicalIF":8.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the effect of recreational fear on inflammation: A prospective cohort field study","authors":"Marie Louise Bønnelykke-Behrndtz ,&nbsp;Mathias Clasen ,&nbsp;Josephine N.E. Benckendorff ,&nbsp;Karoline Assifuah Kristjansen ,&nbsp;Linea Høyer ,&nbsp;Camilla Mensel ,&nbsp;Kumanan Nanthan ,&nbsp;Marc M. Andersen","doi":"10.1016/j.bbi.2024.10.036","DOIUrl":"10.1016/j.bbi.2024.10.036","url":null,"abstract":"&lt;div&gt;&lt;div&gt;A fear reaction is fundamental for survival and naturally activates the adrenergic system, prompting an acute and vital flight-or-fight response. While sustained stress is associated with unhealthy low-grade inflammation, more acute and transient activation of the adrenergic system has been suggested to impact the immune system and subsequently attenuate low-grade inflammation, e.g. through cold exposure or hyperventilation. Voluntary exposure to frightening stimuli, such as scary entertainment, is another reliable activator of the adrenergic system, yet its impact on the immune system and low-grade inflammation is unknown.&lt;/div&gt;&lt;div&gt;The objectives of this study are to i. assess proportional changes of participants with low-grade inflammation at and three days after a voluntary frightening event, and ii. explore mean value alterations in inflammatory markers and immune cells over time.&lt;/div&gt;&lt;div&gt;We recruited adult participants among visitors to a real-life intense frightening haunted house attraction, located in Vejle, Denmark. The overall fright potential of the exposure was estimated through heart rate (HR) monitoring and self-reported levels of fear. Low-grade inflammation (defined as high sensitive C-reactive protein (hs-CRP) &gt; 3 mg/L)) and immune cells (subtypes of leukocytes) were measured from blood samples immediately before, immediately after, and three days after the haunted house event.&lt;/div&gt;&lt;div&gt;A total of 113 participants, 69 females (61.1 %), and 44 males (38.9 %), with a mean age of 29.7 (SD 10.1) were included in the analyses. The average duration of exposure was 50 min and 51 s, while the mean HR throughout the event was 111.1 BPM (mean SD 10.1), and the mean subjective reported scare level was 5.4 (SD 1.9) on a Likert scale ranging from 1 to 9. Twenty-two participants exhibited low-grade inflammation (hs-CRP &gt; 3 mg/L) at the event, with 10 participants normalizing their hs-CRP levels three days post-event. Seven participants had normal hs-CRP levels at the event, but low-grade inflammation three days post-event. Thus, we found no proportional difference between participants with low-grade inflammation at the event (19.5 %) and three days after the event (16.8 %) (diff. −2.7 %; 95 % CI: −10.7 to 5.4, p = 0.47). For the 22 participants exhibiting low-grade inflammation at the event, 18 participants (82 %) decreased their hs-CRP levels, with a mean decrease in hs-CRP from 5.7 mg/L pre-event to 3.7 mg/L three days post-event (diff. −2.0, 95 % CI: −3.2 to −0.7, p = 0.003). Supporting an overall attenuation of inflammation, total leukocytes and lymphocytes decreased for both participants with low-grade inflammation and with normal inflammatory levels, when comparing levels pre- and three days post-event, although all mean levels remained within the normal range.&lt;/div&gt;&lt;div&gt;Conclusively, we find no proportional differences in participants exhibiting low-grade inflammation (hs-CRP &gt; 3) when comparing levels at and thre","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 1042-1051"},"PeriodicalIF":8.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}