PhD Scientific Days 2025

Poster Session I. - F: Pharmaceutical Sciences and Health Technologies

Immune Dysregulation in Clozapine-Induced Myocarditis

Előadó neve

Dr. Jakab Márk

Neptun code

H8Q1UT

Előadó munkahelye

Semmelweis University, Departement of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36306316801

Előadó e-mail címe

jakab.mark@semmelweis.hu

Az előadás címe

Immune Dysregulation in Clozapine-Induced Myocarditis

Szerző(k) neve és munkahelye

Márk E. Jakab^1,2,3,4, Zsombor I. Hegedűs^1,2,3,4, Lilla Szabó^1,2,3,4, Tamás Kovács^1,2,3,4, Andrea Kovács^1,2,3,4, Zoltán V. Varga^1,2,3,4

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2: Center for Pharmacology and Drug Research & Development, Budapest, Hungary
3: HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary
4: MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session I. - F: Pharmaceutical Sciences and Health Technologies

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Pharmacovigilance data identify clozapine, a highly effective antipsychotic for treatment-resistant schizophrenia, as the leading cause of drug-induced myocarditis. No specific treatment exists; discontinuation remains the primary approach, risking psychiatric decompensation. The mechanisms underlying clozapine-induced myocarditis (CIM) remain unclear. Evidence points to eosinophilic infiltration and a Th2-driven immune response, but other factors—including innate lymphoid cells (ILCs) and pro-inflammatory cytokines—may contribute.
Aims: We aimed to characterize the immune alterations in a murine model of CIM, focusing on cytokine expression and immune cell infiltration.
Methods: Male BALB/c mice (8 weeks old) received intraperitoneal injections of clozapine (25 mg/kg or 35 mg/kg) or vehicle control for 21 days. After treatment, cardiac tissue underwent histopathological and transcriptomic analysis to assess inflammatory markers, cytokine gene expression, and leukocyte infiltration.
Results: Clozapine administration induced dose-dependent myocardial inflammation marked by leukocyte infiltration and focal necrosis. Transcriptomic profiling showed increased IL-13, IL-33, and eosinophil-attracting chemokines CCL11 and CCL24 (eotaxins). Elevated IL-17A was also observed, while IFN-γ, TNF-α, and IL-1β remained unchanged.
Conclusion: Our findings indicate that clozapine-induced myocarditis involves immune dysregulation marked by Th2- and Th17-related cytokine signatures without classical pro-inflammatory cytokine upregulation. The concurrent increase in IL-13, IL-33, and eotaxins suggests an eosinophilic and type 2 inflammatory milieu, potentially driven by adaptive and innate lymphoid pathways. This immune profile offers novel mechanistic insights into CIM and a basis for exploring immunomodulatory interventions targeting specific cytokines and cell populations.
Funding: Momentum Research Grant from the Hungarian Academy of Sciences (LP- 2021-38 to ZVV).

University

Semmelweis University

Supervisor

Varga Zoltán

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8002

Start

17:00

End

17:06