The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2

Abstract

Background Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60–90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection. Results Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production. Conclusion The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly. Subjects Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation

Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection

“…The biocompatibility analysis of G2-S16 and G2-S24P dendrimers in peripheral blood mononuclear cell (PBMC) cultures was conducted by MTT and LDH assays in treatments with increasing concentrations (5,10,20, and 50 µM) for 48 h (Figure 1). Concentrations where cell viability exceeded 80% were considered non-toxic in comparison to the nontreated condition [19].…”

“…Particularly, Thymosin-alpha-1 (Tα1) has been shown to play a key role in the control of immunity, tolerance and inflammation, which explains its wide range of clinical applications in several pathologies, including infectious diseases [9]. Recently, we have studied the immunomodulatory effect of Tα1 in a SARS-CoV-2 scenario [10] and during HCMV infection, demonstrating that Tα1 treatment might support its use as an adjuvant for therapeutic treatment with cell therapies or with routine HCMV drugs in immunocompromised patients [11].…”