Immune Modulation with Thymosin Alpha 1 Treatment

King, R. S. B.; Tuthill, Cynthia

doi:10.1016/bs.vh.2016.04.003

Cited by 62 publications

(47 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, Tα1 has been used to treat hepatitis B, resistance to infection and breast cancer ( 13 , 25 , 26 ). Tα1 is a peptide that affects multiple immune subsets associated with immune suppression ( 27 ). Furthermore, previous studies have reported that Tα1 serves a critical function in balancing pro- and anti-inflammatory cytokine production through the involvement of distinct TLRs acting on different dendritic cell subsets and the MyD88-dependent signaling pathway ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure

et al. 2018

View full text Add to dashboard Cite

The present study aimed to evaluate whether thymosin α1 (Tα1) increases survival rates through the improvement of immunofunction and inhibition of hepatocyte apoptosis in rats with acute liver failure (ALF). A total of 25 rats were randomly divided into the control group (CG), the model group (MG) and the treatment group (TG). The CG received an intraperitoneal injection of saline (2 ml). The ALF rat model was established by the intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 µg/kg). The TG received an intraperitoneal injection of Tα1 (0.03 mg/kg) 1 h prior to and 30 min after modeling. The survival rates of the rats were recorded. An additional 63 rats were randomly divided into a CG (n=3), MG (n=30) and TG (n=30). Three rats were sacrificed at 3, 6, 9 and 12 h after establishment of the rat model to detect plasma alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), tumor necrosis factor (TNF)-α and interleukin-10 (IL-10). Liver samples were stained with hematoxylin and eosin and TUNEL, and reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to detect B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in liver tissue. The results indicated that the survival rate of the TG was significantly higher compared with that of the MG at 24 h (P<0.05). Plasma ALT, AST and TBIL in the MG and TG increased over time (3–12 h), with ALT, AST and TBIL observed to be significantly lower in the TG compared with the MG at each time-point (P<0.05). Hepatocellular necrosis, hemorrhage and inflammatory cell infiltration of ALF were aggravated over time (3–12 h) in the MG and TG. Notably, in the Tα1-treated rats, the hepatocytes appeared healthier with fewer apoptotic cells compared with those from the MG at the same time-points. Hepatocyte apoptotic index increased in the TG and MG, but was significantly lower in the TG compared with the MG at each time-point (P<0.05) in TUNEL assays. Plasma TNF-α and IL-10 in the MG and TG increased over time (3–12 h), with TNF-α observed to be significantly lower in the TG compared with the MG at each time-point (P<0.05), however, IL-10 was observed to be significantly higher in the TG compared with the MG at each time-point (P<0.05). Bax mRNA expression was significantly lower in the TG compared with the MG at each time-point (P<0.05), whereas Bcl-2 was significantly higher (P<0.05). In conclusion, Tα1 improved survival rates in an ALF rat model by downregulating TNF-α and upregulating IL-10, leading to the attenuation of hepatic inflammation and hepatocyte apoptosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Based on these data, Tα1 was then used for the treatment of chronic hepatitis B and C (Iino et al, 2005;You et al, 2006), cytomegalovirus infection (Bozza et al, 2007) and invasive aspergillosis (Romani et al, 2004). In addition, the post-marketing data on Zadaxin ® (SciClone) clearly confirmed Tα1 immunomodulatory activities and related therapeutic potential also in cancer (such as Hepatocellular carcinoma, lung cancer, and melanoma), infectious diseases (sepsis, infections after bone marrow transplant, lung infections including chronic obstructive pulmonary disorder, Severe acute respiratory syndrome, and HIV) (King and Tuthill, 2016;Liu et al, 2016a;Matteucci et al, 2017;Jia et al, 2015) and improvement in immune responses of elderly immunocompromised patients (for example for enhancement of response to vaccines) (Tuthill et al, 2012).…”

Section: Thymosins: the Old And The Newmentioning

confidence: 93%

Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application

Severa

Zhang

Giacomini

et al. 2019

Multiple Sclerosis and Related Disorders

View full text Add to dashboard Cite

“…3h and 3j). Thymosin alpha-1 (Tα1), the first 28 amino acids of PTMA, was found to be involved in T cell development, and has been used for the treatment of certain infection diseases including COVID-19 23 . In addition, Tea expressed less PTMA than Te, and Tm-3 expressed the highest level of PTMA in all the sub-clusters of CD8 T cells (Fig.…”

Section: Excessive Activation Led To Exhaustion Of Cd8 T Effector Celmentioning

confidence: 99%

Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

et al. 2020

Preprint

View full text Add to dashboard Cite

Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed dysregulated adaptive immune responses in patients with severe disease. A new cluster of excessively activated CD8 T cells (Tea) was further identified, which displayed exhausted phenotypes and diminished function of antigen recognition. Interestingly, expression of PTMA, the proprotein of Tα1, was significantly increased in a group of highly proliferating CD8 T cells with memory stem cell features. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

show abstract

Immune Modulation with Thymosin Alpha 1 Treatment

Cited by 62 publications

References 89 publications

Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure

Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure

Thymosins in multiple sclerosis and its experimental models: moving from basic to clinical application

Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

Contact Info

Product

Resources

About