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

Salomao, Reinaldo [UNIFESP]; Brunialti, Milena K. C. [UNIFESP]; Gomes, Natalia E. [UNIFESP]; Mendes, Marialice E. [UNIFESP]; Diaz, Ricardo Sobhie [UNIFESP]; Komninakis, Shirley [UNIFESP]; Machado, Flavia R. [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Rigato, Otelo [UNIFESP]

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

Data

2009-01-01

Autores

Salomao, Reinaldo

Brunialti, Milena K. C.

Gomes, Natalia E.

Mendes, Marialice E.

Diaz, Ricardo Sobhie

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Artigo

Resumo

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)

Citação

Critical Care Medicine. Philadelphia: Lippincott Williams & Wilkins, v. 37, n. 1, p. 132-139, 2009.