Effects of Combined Treatment with Sodium Dichloroacetate and Sodium Valproate on the Genes in Inflammation- and Immune-Related Pathways in T Lymphocytes from Patients with SARS-CoV-2 Infection with Pneumonia: Sex-Related Differences

Author:

Stakišaitis Donatas12,Kapočius Linas1,Tatarūnas Vacis3,Gečys Dovydas3,Mickienė Auksė4,Tamošuitis Tomas5,Ugenskienė Rasa6,Vaitkevičius Arūnas7,Balnytė Ingrida1,Lesauskaitė Vaiva3

Affiliation:

1. Department of Histology and Embryology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania

2. Laboratory of Molecular Oncology, National Cancer Institute, 08660 Vilnius, Lithuania

3. Institute of Cardiology, Laboratory of Molecular Cardiology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania

4. Department of Infectious Diseases, Lithuanian University of Health Sciences, 47116 Kaunas, Lithuania

5. Department of Intensive Care Medicine, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania

6. Department of Genetics and Molecular Medicine, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania

7. Institute of Clinical Medicine, Faculty of Medicine, Vilnius University Hospital Santaros Klinikos, Vilnius University, 08661 Vilnius, Lithuania

Abstract

The study presents data on the anti-inflammatory effects of a combination of sodium dichloroacetate and sodium valproate (DCA–VPA) on the expression of inflammation- and immune response-related genes in T lymphocytes of SARS-CoV-2 patients. The study aimed to assess the effects of DCA–VPA on the genes of cytokine activity, chemokine-mediated signaling, neutrophil chemotaxis, lymphocyte chemotaxis, T-cell chemotaxis, and regulation of T-cell proliferation pathways. The study included 21 patients with SARS-CoV-2 infection and pneumonia: 9 male patients with a mean age of 68.44 ± 15.32 years and 12 female patients with a mean age of 65.42 ± 15.74 years. They were hospitalized between December 2022 and March 2023. At the time of testing, over 90% of sequences analyzed in Lithuania were found to be of the omicron variant of SARS-CoV-2. The T lymphocytes from patients were treated with 5 mmol DCA and 2 mmol VPA for 24 h in vitro. The effect of the DCA–VPA treatment on gene expression in T lymphocytes was analyzed via gene sequencing. The study shows that DCA–VPA has significant anti-inflammatory effects and apparent sex-related differences. The effect is more potent in T cells from male patients with SARS-CoV-2 infection and pneumonia than in females.

Funder

European Regional Development Fund

Publisher

MDPI AG

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