Dataset Information

Interleukin-1 Beta-Mediated Sex Differences in Kawasaki Disease Vasculitis Development and Response to Treatment.

ABSTRACT:

Objective

Kawasaki disease (KD) is the leading cause of acute vasculitis and acquired heart disease in children in developed countries. Notably, KD is more prevalent in males than females. We previously established a key role for IL (interleukin)-1 signaling in KD pathogenesis, but whether this pathway underlies the sex-based difference in susceptibility is unknown. Approach and Results: The role of IL-1 signaling was investigated in the Lactobacillus casei cell wall extract-induced experimental mouse model of KD vasculitis. Five-week-old male and female mice were injected intraperitoneally with PBS, Lactobacillus caseicell wall extract, or a combination of Lactobacillus caseicell wall extract and the IL-1 receptor antagonist Anakinra. Aortitis, coronary arteritis inflammation score and abdominal aorta dilatation, and aneurysm development were assessed. mRNA-seq (messenger RNA sequencing) analysis was performed on abdominal aorta tissue. Publicly available human transcriptomics data from patients with KD was analyzed to identify sex differences and disease-associated genes. Male mice displayed enhanced aortitis and coronary arteritis as well as increased incidence and severity of abdominal aorta dilatation and aneurysm, recapitulating the increased incidence in males that is observed in human KD. Gene expression data from patients with KD and abdominal aorta tissue of Lactobacillus caseicell wall extract-injected mice showed enhanced Il1b expression and IL-1 signaling genes in males. Although the more severe IL-1?-mediated disease phenotype observed in male mice was ameliorated by Anakinra treatment, the milder disease phenotype in female mice failed to respond.

Conclusions

IL-1? may play a central role in mediating sex-based differences in KD, with important implications for the use of anti-IL-1? therapies to treat male and female patients with KD.

SUBMITTER: Porritt RA

PROVIDER: S-EPMC7047651 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Interleukin-1 Beta-Mediated Sex Differences in Kawasaki Disease Vasculitis Development and Response to Treatment.

Porritt Rebecca A RA Markman Janet L JL Maruyama Daisuke D Kocaturk Begum B Chen Shuang S Lehman Thomas J A TJA Lee Youngho Y Fishbein Michael C MC Noval Rivas Magali M Arditi Moshe M

Arteriosclerosis, thrombosis, and vascular biology 20200130 3

<h4>Objective</h4>Kawasaki disease (KD) is the leading cause of acute vasculitis and acquired heart disease in children in developed countries. Notably, KD is more prevalent in males than females. We previously established a key role for IL (interleukin)-1 signaling in KD pathogenesis, but whether this pathway underlies the sex-based difference in susceptibility is unknown. Approach and Results: The role of IL-1 signaling was investigated in the <i>Lactobacillus casei</i> cell wall extract-induc ...[more]

PMID: 31996019

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Project description:Introduction:Tinnitus is a complex symptom requiring a thorough multidisciplinary assessment to construct an individual's tinnitus profile. The Antwerp University Hospital hosts a tertiary tinnitus clinic providing intensive, multidisciplinary tinnitus care in the form of combinational psychological treatment with either Tinnitus Retraining Therapy (TRT)/Cognitive Behavioral Therapy (CBT) or TRT/eye movement desensitization and reprocessing therapy (EMDR), high-definition transcranial direct current stimulation (HD-tDCS), and physical therapy treatment (in cases of somatic influence of the neck or the temporomandibular area). Several factors may contribute to therapy effect of which the role of gender has recently gained more interest. As such, the current manuscript explores gender differences in the outcome of different tinnitus treatments. Methods:Data on treatment outcome of four distinct tinnitus treatments (1. HD-tDCS; 2. orofacial physical therapy; 3. combination TRT + CBT; and 4. combination TRT + EMDR) were pooled and compared. Treatment outcome was assessed via the Tinnitus Functional Index (TFI). Participants completed the TFI at baseline, immediately after treatment and after 9 weeks (±3 weeks) follow-up. To explore the effect of gender on different treatment outcomes, a linear mixed model was designed including Time point, Gender, and Therapy Group as fixed factors as well as all interactions between these factors. Results:TFI scores improved significantly over time regardless of therapy group (p < 0.0001). A mean TFI decrease of at least 13 points was obtained by all participants except by those in the HD-tDCS. Significant interactions between Gender and Time point were identified in all groups except for the TRT +EMDR group. Female subjects improved more extensively than males in the HD-tDCS (p = 0.0009) and orofacial therapy group (p = 0.0299). Contrarily, in the TRT +CBT group, male participants showed a significant improvement whereas the mean TFI scores of female subjects remained on baseline levels (p = 0.0138). Conclusion:Our data suggest that male and female tinnitus patients seem to react differently to different therapy options. We strongly encourage further prospective studies to discern the relevance of gender in therapy outcome.

Dataset Information

Interleukin-1 Beta-Mediated Sex Differences in Kawasaki Disease Vasculitis Development and Response to Treatment.

Objective

Conclusions

Publications

Interleukin-1 Beta-Mediated Sex Differences in Kawasaki Disease Vasculitis Development and Response to Treatment.

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