Toll-like Receptor Kinetics in Septic Shock Patients: A Preliminary Study

Abstract

The aim of this study is to evaluate some inflammatory parameter changes in septic shock patients and their possible correlation with clinical outcome, in particular when continuous veno-venous hemofiltration (CVVH) treatment is required. Considering the objective difficulty in enrolling this kind of patient, a preliminary study was initiated on seventeen septic shock patients admitted to a medical and surgical ICU. The mRNA expression of Toll-like receptor (TLR)-1, TLR-2, TLR-4, TLR-5, TLR-9, TNFα, IL-8 and IL-1β was assessed, the plasmatic concentrations of IL-18, IL-2, IL-10 and TNFα were measured on the day of sepsis diagnosis and after 72 h. In those patients who developed acute renal failure unresponsive to medical treatment and who underwent CVVH treatment the same parameters were measured every 24 h during CVVH and after completion of the treatment. On sepsis diagnosis, gene expression of TLRs was up-regulated compared to the housekeeping gene in all the patients. After 72 h, in 35% of the patients a down-regulation of these genes was found compared to day 1, but it was not associated with a reduction of cytokine serum levels or improved clinical signs, better outcome or reduced mortality. After high volume hemofiltration treatment, cytokine serum levels and TLR expression were not significantly modified. In conclusion, considering the not numerous number of cases, from our preliminary study, we cannot certainly correlate TLR over-expression in septic shock patients with severity or outcome scores.

Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway

“…The LPS-induced overexpression of TLR4 is associated with changes in the levels of inflammatory mediators. Accumulating evidence has suggested that LPS-induced overactivation of the TLR4 signaling pathway leads to an increase in the production of pro-inflammatory mediators, with fatal consequences to the host (21)(22)(23). The results of the present study demonstrated that exposure to 20 mg/kg LPS increased the expression levels of TLR4 in mice colon tissue.…”

“…The TLR4 receptor detects foreign antigens and initiates the innate immune response. The ability of TLR4 to rapidly detect pathogens is key to the inflammatory response initiated in patients with severe sepsis (21). The LPS-induced overexpression of TLR4 is associated with changes in the levels of inflammatory mediators.…”

The Relationship Between Sepsis-induced Immunosuppression and Serum Toll-like Receptor 9 Level

“…In a septic-shock study, investigators found that 35% of patients had a down-regulation of TLR gene expression compared to their baseline values (32). We are of the opinion that the low levels of serum TLR9 detected in our study were because of down-regulation in these sepsis cases.…”

Toll-Like Receptor 2 in Serum: a Potential Diagnostic Marker of Prosthetic Joint Infection?

“…TLR2 has been described to be crucial in joint infection (20), contributing to the degenerative process and destructive arthropathy after microbial joint infection (23), indicating that TLR2 expression strictly reflects the progression of the infection in the host. So far, the alteration of TLR2 and TLR4 has been evaluated only at the gene expression level (24,25), while the present work is the first, to our knowledge, which measures the amount of circulating protein, making it suitable for routine clinical diagnosis. In order to evaluate TLR2 circulating levels as diagnostic tools, we compared them with canonical markers of infection and inflammation.…”