Role of Toll-like receptor-4 and soluble Toll-like receptor-4 in the pathogenesis of Gram-negative sepsis

Abstract

Introduction Sepsis is a serious inflammatory clinical syndrome with poor outcome, triggered mostly by Gram-negative infections. Dysregulated Toll-like receptor-4 (TLR4)-mediated innate responses play a role in the pathogenesis of sepsis. Aim of work This study aimed to evaluate the levels of expression of TLR4 on neutrophils and monocytes in patients with different degrees of sepsis, to estimate serum levels of soluble TLR4 (sTLR4), tumor necrosis factor (TNF)-α and C-reactive protein (CRP) in these patients and to compare these results with those of controls and to correlate the results with disease severity and outcome. Patients and methods Ninety individuals were included. Forty five patients were classified into 2 groups (35 with sepsis and 10 with septic shock); all patients were selected from among systemic inflammatory syndrome (SIRS) patients admitted to the Intensive Care Unit after positive blood culture for Gram-negative bacilli. A total of 45 healthy controls were also recruited. All participants were subjected to the following investigations: evaluation of expression of TLR4 on neutrophils and monocytes (by flow cytometry) and determination of serum levels of sTLR4 and TNF-α (by enzyme-linked immunosorbent assay) and quantitative CRP (qCRP; by turbidimetry). Results were correlated with disease severity and outcome. Results The most common isolated organism was Klebsiella pneumoniae (40%). Among all the isolated organisms, 56.6% were multi-drug resistant. The most common primary site of infection was the lower respiratory tract. Out of the 45 patients studied, 30 patients died. In both patient subgroups, compared with the controls, the following was observed: a significant increase in TLR4 expression on neutrophils and monocytes (P<0.001), increased levels of sTLR4 (P<0.001), qCRP (P<0.001), and a non-significant difference in TNF-α (P=0.128). Conclusion Increased levels of sTLR4 are accompanied by reduced levels of TNF-α, but not qCRP, in patients with sepsis. TLR4 and sTLR4 may be useful diagnostic markers for identifying patients with sepsis among SIRS patients.