Moderate · human
This open-label randomized controlled trial (NCT03082885) enrolled 73 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), randomizing them to standard medical therapy (SMT, n=38) or SMT plus Thymosin α1 (Tα1, n=35), with a primary endpoint of 90-day transplant-free survival. Using flow cytometry and ELISA, researchers characterized peripheral immune cell subsets and serum cytokines at baseline and over follow-up. The study found that 90-day survivors had higher baseline effector T (TE) cell proportions, lower regulatory T cells (Tregs), and higher pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) compared to non-survivors. Non-survivors developed a progressive hyperinflammatory trajectory over time. Tα1 treatment was associated with improved 90-day transplant-free survival, reduced Treg frequencies (including CD226 low/- Treg subsets) at weeks 4–8, and moderation of late-stage hyperinflammation without suppressing early immune activation. The authors conclude Tα1 may rebalance immune responses in ACLF. Key limitations include the open-label design, relatively small sample size, and a single-center context, which may limit generalizability.
Immunopharmacology and immunotoxicology · Mar 2026DOI ↗ Moderate · humanPreprint
This single-center randomized controlled trial enrolled 171 elderly patients with sepsis-associated acute respiratory distress syndrome (ARDS) to evaluate whether adding thymosin alpha 1 (Tα1) to a background regimen of sivelestat sodium and ambroxol improved outcomes. Participants were assigned to a control group (sivelestat + ambroxol, n=86) or an experimental group (same regimen plus Tα1, n=85) for 7 days; all patients also received high-flow nasal cannula oxygen therapy. The study found that the experimental group demonstrated a higher overall clinical response rate (85.9% vs. 72.1%, P<0.05), reduced mortality, improved survival, and better respiratory function parameters compared with controls. Safety profiles were reported as favorable in both groups. Limitations include the single-center design, which may reduce generalizability; the relatively short 7-day intervention window; and the fact that the paper is a preprint, meaning it has not yet undergone formal peer review. The combination of co-interventions (sivelestat and ambroxol alongside Tα1) also makes it difficult to isolate the independent contribution of Tα1 to the observed outcomes.
Unknown journal · Sep 2025DOI ↗ Moderate · human
This systematic review and meta-analysis evaluated the efficacy of thymosin α1 (Tα1), a synthetic immunomodulatory peptide, in treating sepsis. Researchers searched for prospective clinical studies measuring 28-day mortality in sepsis patients treated with Tα1 (excluding combination therapy studies), ultimately including 11 randomized controlled trials (RCTs) totaling 1,927 patients. The overall meta-analysis found a statistically significant reduction in 28-day mortality associated with Tα1 (OR 0.73, 95% CI: 0.59–0.90). However, when analysis was restricted to high-quality trials or multicenter trials — considered more rigorous subsets — the mortality benefit was no longer statistically significant (ORs 0.82 and 0.86, respectively). A heterogeneity of treatment effects analysis drawing on individual patient data from two large multicenter RCTs (representing ~75% of total patients) suggested potential benefits in subgroups with cancer (moderate credibility), diabetes, and coronary heart disease (both low credibility). Trial sequential analysis indicated the current evidence base is underpowered. The authors concluded that while Tα1 shows potential, its benefits appear to vary across patient subgroups, and personalized immunotherapy approaches warrant investigation in future, adequately powered trials.
Frontiers in cellular and infection microbiology · Sep 2025DOI ↗ Moderate · human
This systematic review and meta-analysis evaluated the efficacy of Thymosin alpha 1 (Tα1), an immunomodulatory peptide, in patients with severe acute pancreatitis (SAP). Researchers searched five major databases through February 2025 and identified five randomized controlled trials encompassing 706 SAP patients, comparing Tα1 treatment against non-Tα1 controls. The pooled analysis found that Tα1 was associated with increased percentages of CD4+ T cells and improved CD4+/CD8+ ratios, suggesting a positive effect on immune cell balance and reduction of immune suppression. Lower-dose Tα1 was associated with significantly reduced C-reactive protein (CRP) levels, an inflammation marker. Tα1 was also associated with a potential reduction in extrapancreatic infection risk. The authors concluded that Tα1 may regulate immune cell balance and exert anti-inflammatory effects in SAP patients, potentially improving prognosis. Key limitations include the small number of included trials (n=5), the relatively modest total patient population, heterogeneity in dosing protocols, and the predominance of studies from a single country (China), which may limit generalizability. The authors noted that further research is needed to validate these findings.
Frontiers in immunology · Jun 2025DOI ↗