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

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)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Dept Intens Care, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Dept Gynecol, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Dept Intens Care, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Escola Paulista Med, Dept Gynecol, São Paulo, BrazilFAPESP: 04/15548-2CNPq: 305101/2002-1CNPq: 479666/2004-0Web of Scienc