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

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.

Differential Impact of Valproic Acid on SLC5A8, SLC12A2, SLC12A5, CDH1, and CDH2 Expression in Adult Glioblastoma Cells

“…Elucidating the evolution of GBM sex-linked dimorphism and the efficacy of treatments will be essential to improve the effectiveness of treatment and patient survival, and ensuring that personalized treatment based on specific molecular mechanisms of GBM is an essential challenge for further research [18]. Treatment with a combination of VPA and dichloroacetate significantly increased Slc5a8 gene expression and showed a significant anti-inflammatory effect on thymocytes from male mice [19], and treatment of T lymphocytes from males and females with this combination showed a significant anti-inflammatory effect and gender-related differences [20]. It was reported that different VPA effect the expression of the SLC12A2 (NKCC1) and SLC12A5 (KCC2) co-transporter genes in pediatric glioblastoma PBT24 (boys) and SF8628 (girls) cells [21].…”