Editor’s Note: With growing attention to immunotherapy, thymosin alpha-1 (Tα1), a bioactive peptide composed of 28 amino acids with immunomodulatory effects, is increasingly applied in infectious diseases and critical care. Tα1 mainly enhances cellular and humoral immunity by promoting T-cell development and maturation. It has thus gained widespread application in managing infections and critical illnesses, backed by significant evidence from clinical studies. Recently, the National Clinical Research Center for Infectious Diseases and the National Center for Infectious Diseases released the "Expert Consensus on the Clinical Application of Thymosin Alpha-1 in Infectious Diseases and Critical Illness" (referred to as the “Consensus”), offering ten recommended applications of Tα1 for liver disease, viral and bacterial infections, and severe infections. At the recent "National Key Laboratory Conference on Diagnosis and Treatment of Zoonotic Infectious Diseases and the 6th Central Academic Conference on Liver Diseases and Infections (CCIFLDI 2024)," Dr. Tao Chen from Tongji Hospital, provided an in-depth interpretation of the Consensus.Overview of Thymosin Alpha-1 (Tα1)
Thymosin Alpha-1 (Tα1), also known as thymic peptide α1, was initially isolated from calf thymus and is expressed in humans with an identical sequence. Tα1 enhances the immune response to viruses, bacteria, and tumors, and has long been recognized as an immune enhancer and immunomodulator. By directly or indirectly influencing various immune cells, Tα1 supports both innate and adaptive immunity, helping to defend against external pathogens and eliminate toxic endogenous substances like tumor cells.
Additionally, Tα1 can stimulate precursor T cells and promote the transformation of Th lymphocytes into the Th1 subtype, increasing cytokines such as IL-2 and IFN-γ and the count of CD8+ T cells. Tα1 also stimulates natural killer (NK) cells and macrophages to exert anti-infective and anti-tumor activity. Furthermore, Tα1’s regulatory functions reduce inflammatory cytokine storms by increasing regulatory T cells and suppressive cytokines like IL-10.
The Consensus bases its recommendations on domestic and international evidence to provide clinical guidance.
Key Recommendations from the Consensus
- Recommendation 1: Thymosin Alpha-1 in Hepatitis B-related Cirrhosis
Thymosin Alpha-1 combined with entecavir improves fibrosis markers in hepatitis B-related cirrhosis and reduces mortality in cirrhotic patients with spontaneous bacterial peritonitis (A2).
- Recommendation 2: Thymosin Alpha-1 in Hepatitis B-related Liver Failure
Thymosin Alpha-1 treatment in intermediate- to late-stage HBV-ACLF patients can reduce secondary infection rates and improve survival rates (B1).
- Recommendation 3: Thymosin Alpha-1 in Chronic Hepatitis B Treatment
Thymosin Alpha-1 is safe and well-tolerated, with synergistic effects in suppressing HBV replication in chronic hepatitis B patients, warranting further study in combination therapies (B2).
- Recommendation 4: Thymosin Alpha-1 in COVID-19
Early use of Tα1 in COVID-19 patients can reduce severe cases, shorten hospitalization time, and improve recovery rates, especially in elderly or immunocompromised patients (B1).
- Recommendation 5: Thymosin Alpha-1 in Bacterial and Fungal Lung Infections
Tα1 modulates T-cell subsets, enhances immune function, and has shown efficacy and safety in improving blood gas and lung function in severe pneumonia patients (B2).
- Recommendation 6: Thymosin Alpha-1 in Tuberculosis
In tuberculosis with diabetes, Tα1 combined with anti-TB treatment significantly enhances immune response, lowers inflammatory cytokine levels, and improves efficacy (B2).
- Recommendation 7: Thymosin Alpha-1 in Sepsis
Tα1 improves immune function and reduces mortality in sepsis patients (B2), as shown in the ETASS study, which included ICU patients with severe sepsis.
- Recommendation 8: Thymosin Alpha-1 in Severe Acute Pancreatitis
Routine Tα1 use is not recommended, but it may reduce the risk of infectious pancreatic necrosis in SAP patients with hyperglycemia or low lymphocyte counts (C2).
- Recommendation 9: Thymosin Alpha-1 in Infection Prevention for Cancer Patients
Tα1 has been shown to improve immune function, reduce hospital-acquired infection rates, enhance quality of life, and improve survival rates in cancer patients (B2).
- Recommendation 10: Thymosin Alpha-1 in Enhancing Vaccine Response in Elderly and Immunocompromised Patients
Tα1 enhances immune response to vaccines in elderly and immunocompromised individuals, improving antibody levels post-vaccination (B1).
Future Directions and Unresolved Questions
- Safety and Efficacy: Further clinical trials are needed to assess Tα1’s safety and efficacy.
- Optimal Dosage and Timing: Research is needed to determine the best dosage and timing for Tα1 treatment.
- Predictive Biomarkers: Identifying biomarkers that predict patient response to Tα1 could aid in personalizing treatment.
- Combination Therapies: Combining Tα1 with other immunotherapies or chemotherapies could enhance efficacy and reduce side effects.
- Mechanistic Insights: Understanding Tα1’s molecular mechanisms could inform future treatments and target discovery.
- Long-term Outcomes: More studies are needed to assess long-term survival and potential adverse effects following Tα1 treatment.
- Cost-effectiveness: The high production cost of Tα1 may affect its accessibility in resource-limited settings.
- Real-world Evidence: Real-world data is essential to evaluate Tα1’s safety, efficacy, and cost-effectiveness.
Dr. Chen’s insights highlight Tα1’s potential across diverse conditions, especially in enhancing patient outcomes in infectious and critical care contexts, and underscore the need for ongoing research to optimize its use.
