Toll-like receptor pathway signaling is differently regulated in neutrophils and peripheral mononuclear cells of patients with sepsis, severe sepsis, and septic shock

Author(s)

Salomao, Reinaldo ^[1] ; Brunialti, Milena K. C. ^[1] ; Gomes, Natalia E. ^[1] ; Mendes, Marialice E. ^[1] ; Diaz, Ricardo S. ^[1] ; Komninakis, Shirley ^[1] ; Machado, Flavia R. ^[2] ; Guerreiro da Silva, Ismael D. C. ^[3] ; Rigato, Otelo ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP, Escola Paulista Med, Div Infect Dis, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, UNIFESP, Escola Paulista Med, Dept Intens Care, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, UNIFESP, Escola Paulista Med, Dept Gynecol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Critical Care Medicine; v. 37, n. 1, p. 132-139, JAN 2009.
• Web of Science Citations: 35

Abstract

Objectives: Up- and down-regulation of inflammatory response was described in blood cells from septic patients, according to the stage of sepsis and the cells evaluated. This study aimed to evaluate the Toll-like receptor (TLR) signaling pathway gene expression in peripheral blood mononuclear cells (PBMC) and neutrophils in patients throughout the different stages of sepsis. Design: Prospective, observational study. Settings. Two emergency rooms and two intensive care units in one university and one teaching hospital. Patients and Controls., A total of 15 septic patients, five with sepsis, five with severe sepsis, and five with septic shock, in addition to five healthy volunteers were enrolled. Interventions: None. Measurements and Main Results: The Human-TLR Signaling Pathway, which comprises 84 genes related to TLR-mediated signal transduction, was evaluated by real time polymerase chain reaction in PBMC and neutrophils obtained from patients and controls. The fold change for each gene (2((-Delta Delta Ct))) was compared between the groups. Genes with fold changes greater than 2 and significant changes in Delta CT are reported as differently expressed. The told change ratios in PBMC gene expression between septic patients and healthy controls revealed a dynamic process according to the stage of sepsis, tending toward down-regulation of the TLR signaling pathway in PBMC in the more severe forms of the disease. However, the differential gene expression was restricted to five down-regulated genes in septic shock patients, which are found in the effector and downstream pathways. Neutrophils showed a different pattern of adaptation. Patients with sepsis, severe sepsis, and septic shock presented a broad gene upregulation, which included all functional groups evaluated and persisted throughout the stages of the disease. Conclusions: TLR-signaling pathway genes are differently regulated in PBMC and neutrophils of septic patients, and are dynamically modulated throughout the different stages of sepsis. (Grit Care Med 2009; 37:132-139) (AU)