Novel evidence of Thymosin α1 immunomodulatory properties in SARS-CoV-2 infection: Effect on innate inflammatory response in a peripheral blood mononuclear cell-based in vitro model.
Ricci. Daniela D; Etna. Marilena Paola MP; Severa. Martina M; Fiore. Stefano S; Rizzo. Fabiana F; Iannetta. Marco M; Andreoni. Massimo M; Balducci. Stefano S; Stefanelli. Paola P; Palamara. Anna Teresa AT; Coccia. Eliana Marina EM
Key Findings
- Thymosin‑alpha‑1 reduced release of pro‑inflammatory cytokines TNF‑α, IL‑6 and IL‑8 in SARS‑CoV‑2‑stimulated PBMCs
- It increased the anti‑inflammatory cytokine IL‑10 in the same setting
- The peptide dampened activation markers on inflammatory monocytes and myeloid dendritic cells
Practical Outcomes
- The findings suggest thymosin‑alpha‑1 could be a useful immune‑modulating supplement to blunt excessive inflammation during viral infections like COVID‑19. However, because the work is limited to cell cultures, there are no concrete dosage or safety guidelines for self‑administration, so anyone considering it should wait for human studies or consult a medical professional.
Summary
This study shows that the peptide thymosin‑alpha‑1 can calm down the early immune over‑reaction seen in COVID‑19 by lowering harmful inflammatory signals and boosting a calming signal, at least in lab‑grown blood cells. It doesn’t give dosing tips or human trial results, but it supports the idea that Tα1 might help manage the “cytokine storm” during viral infections.
Abstract
The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection. Interestingly, recent papers also demonstrated its mitigating effect on the "cytokine storm" as well as on the T-cell exhaustion/activation in SARS-CoV-2 infected individuals. Nevertheless, in spite of the increasing knowledge on Tα1-induced effects on T cell response confirming the distinctive features of this multifaceted peptide, little is known on its effects on innate immunity during SARS-CoV-2 infection. Here, we interrogated peripheral blood mononuclear cell (PBMC) cultures stimulated with SARS-CoV-2 to disclose Tα1 properties on the main cell players of early response to infection, namely monocytes and myeloid dendritic cells (mDC). Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an increased percentage of CD16<sup>+</sup> inflammatory monocytes and mDC expressing CD86 and HLA-DR activation markers in response to SARS-CoV-2 stimulation. Interestingly, the treatment of SARS-CoV-2-stimulated PBMC with Tα1 dampened the inflammatory/activation status of both monocytes and mDC by reducing the release of pro-inflammatory mediators, including TNF-α, IL-6 and IL-8, while promoting the production of the anti-inflammatory cytokine IL-10. This study further clarifies the working hypothesis on Tα1 mitigating action on COVID-19 inflammatory condition. Moreover, these evidence shed light on inflammatory pathways and cell types involved in acute SARS-CoV-2 infection and likely targetable by newly immune-regulating therapeutic approaches.
Study Information
pubmed
2023
2023-03-13T00:00:00.000Z
10.1016/j.intimp.2023.109996
4
61