The efficacy of thymosin α1 as immunomodulatory treatment for sepsis: a systematic review of randomized controlled trials

Background: Thymosin alpha 1 (T alpha 1) as immunomodulatory treatment is supposed to be beneficial for the sepsis patients by regulating T cell subsets and inflammatory mediators. However, limited by the small sample size and the poor study design, the persuasive power of the single clinical studies is weak. This meta-analysis aimed to investigate the impact of T alpha 1 on the sepsis patients. Methods: We searched for the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CBM, VIP, CNKI, WANFANG, Igaku Chuo Zasshi (ICHUSHI) and Korean literature databases reporting the effects of T alpha 1 on outcomes in sepsis patients. Results: Among 444 related articles, 19 randomized controlled trials (RCTs) met our inclusion criteria. Mortality events were reported in 10 RCTs included 530 patients, and the meta-analysis showed significant decrease in T alpha 1 group compared with control group (RR 0.59, 95 % CI 0.45 to 0.77, p = 0.0001). The subgroup analysis showed no difference between the two dosages (RR 0.59, 95 % CI 0.43 to 0.81; RR 0.59, 95 % CI 0.35 to 0.98, respectively). In 9 RCTs, with a total of 489 patients, T alpha 1 administered once per day decrease APACHE II score significantly (SMD -0. 80, 95 % CI -1.14 to -0.47, p < 0.0001) while T alpha 1 twice per day showed no effect (SMD 0.30, 95 % CI-0.10 to 0.70, p = 0.14). However, the length of ICU stay, the incidence of multiple organ failure (MOF) and duration of mechanical ventilation were not significantly affected by T alpha 1 treatment (SMD -0.52, 95 % CI -1.06 to 0.11, p = 0.06; SMD -0.49, 95 % CI -1.09 to 0.11, p = 0.11; SMD -0.37, 95 % CI -0.90 to 0.17, p = 0.17, respectively). As to the immunological indicators, the level of HLA-DR were increased by T alpha 1 (SMD 1.23, 95 % CI 0.28 to 2.18, p = 0.01) according to the pooled analysis of 8 studies involving 721 patients. Lymphocyte subsets CD3, CD4 and cytokines IL-6, IL-10 and TNF-alpha were also beneficially affected by T alpha 1 treatment. Conclusions: T alpha 1 may be beneficial to sepsis patients in reducing mortality and modulating inflammation reactions. However, the quality of evidence supporting the effectiveness is low considering the small sample sizes and inadequate adherence to standardized reporting guidelines for RCTs among the included studies.