Restoration of Monocyte HLA-DR in Sepsis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Introduction. Sepsis usually develops into an immunosuppressive 
state characterized by a reduction in monocyte HLA-DR expression. 
There have been many immunomodulatory and extracorporeal 
treatment options proposed to overcome this malfunction, but 
their overall effectiveness has not been determined.
Methods. Randomized controlled trials were meta-analysed and 
systematically reviewed to evaluate therapies to restore monocyte 
HLA-DR expression in patients with sepsis in the adult population. 
Trials reporting quantitative post-treatment monocyte HLA-DR 
at an early follow-up time point were included. A random-effects 
model was used to pool standardized mean differences to control 
the heterogeneity among assay platforms.
Results. Seven randomized clinical trials included eight treatment 
groups to be analyzed (a total of 329 subjects). All interventions 
(cytokine-based interventions, granulocyte-macrophage colony
stimulating factor, interferon-γ, extracorporeal modalities, 
polymyxin-B hemoperfusion, continuous hemofiltration, 
hemofiltration–hemoadsorption) resulted in an increase in 
monocyte HLA-DR expression compared to control conditions. 
The overall effect size was large and statistically significant 
(SMD = 1.79, 95% CI: 1.18 to 2.40). Heterogeneity was high (I² ≈ 
78%); however, leave-one-out sensitivity analyses demonstrated 
the robustness of the results, and the direction of the effect was 
always positive across all studies.
Conclusions. Immunomodulatory and extracorporeal therapies 
consistently increase monocyte HLA-DR expression in sepsis, 
supporting the reversibility of sepsis-induced immunosuppression, 
with cytokine-based therapies showing the strongest effects. 
HLA-DR emerges as a key biomarker and therapeutic target, but 
evidence is limited by small, heterogeneous studies and reliance 
on surrogate endpoints. Larger, standardized trials with patient
centred outcomes are needed to determine whether HLA-DR 
restoration improves survival.