Thymosin α1-Based Immunomodulatory Therapy for Sepsis: A Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials

Abstract

Background: Preclinical studies suggest that thymosin α1 has immunoregulatory and anti-inflammatory properties in various septic models. However, whether these effects will transform into improved outcomes in humans with sepsis remains unclear. We performed a meta-analysis to define the role of thymosin α1-based immunomodulatory therapy in sepsis. Methods: We searched Medline and Embase to identify randomized controlled trials that assessed the effect of thymosin α1-based immunomodulatory therapy compared with standard care for adults with sepsis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) using a random-effects model. The primary outcome was 28-day mortality. Results: Nine articles with 10 trials involving 1425 patients were included. Compared with standard care, thymosin α1-based immunomodulatory therapy was associated with a significant 31% relative risk reduction of 28-day mortality (RR 0.69, 95% CI 0.60-0.80, P<0.001), with no statistical heterogeneity (I 2 =0% ). The benefit was confirmed by trial sequential analysis and was consistent across all subgroup analyses. For secondary outcomes, thymosin α1-based immunomodulatory therapy was associated with shorter length of intensive care unit (ICU) stay and duration of mechanical ventilation, increased T lymphocyte subsets (CD3 + , CD4 + , and CD4 + /CD8 + ), and decreased inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and interleukin-6). Conclusions: Thymosin α1-based immunomodulatory therapy decreases 28-day mortality in patients with sepsis. The benefit might be attributed to its immunomodulatory and anti-inflammatory effects. However, caution should be used to translate these findings to clinical practice, because current evidence is potentially subject to bias. Hence, high-quality and adequately powered trials are still warranted.

The severe COVID-19: A sepsis induced by viral infection? And its immunomodulatory therapy

“…A meta-analysis in 2017 on the treatment of sepsis with Ta1 showed that the 28-day mortality was reduced about 30% ( RR = 0.69, 95% CI : 0.60–0.80, p < 0.0001), and CD3+, CD4+, CD4+/CD8+ were significantly increased, and the levels of TNFa, IL-1 beta and IL-6 were significantly decreased, suggesting that Ta1 does not only cause no inflammatory rebound, but also may inhibit the release of proinflammatory cytokines. 68 No clear explanation for that, it maybe that Ta1 ensured the pathogens were more effectively cleared by means of improving the immune function, therefore weakened the inflammatory response. Moreover, Ta1 may be involved in a negative immunomodulatory effects.…”