Effects of simvastatin on cytokines secretion from mononuclear cells from critically ill patients with acute kidney injury

• Autor(a) principal: Ferrari, Gabriela Laender [UNIFESP]
• Data de Publicação: 2011
• Outros Autores: Quinto, Beata Marie [UNIFESP], Queiroz, Kelly Cristina Batista de Souto [UNIFESP], Iizuka, Ilson Jorge, Monte, Julio Cesar Martins [UNIFESP], Dalboni, Maria Aparecida [UNIFESP], Durão, Marcelino de Souza [UNIFESP], Cendoroglo Neto, Miguel [UNIFESP], Santos, Oscar Fernando Pavão dos [UNIFESP], Batista, Marcelo Costa [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/00130000156n1
• DOI: 10.1016/j.cyto.2011.02.005
• Texto Completo: http://dx.doi.org/10.1016/j.cyto.2011.02.005; http://repositorio.unifesp.br/handle/11600/33646
• topic: Simvastatin; Inflammation; Cytokines; Sepsis; AKI

Purpose: To assess the in vitro effects of simvastatin on IL-10 and TNF-alpha secretion from peripheral blood mononuclear cells (PBMC) of critically ill patients with and without acute kidney injury (AKI).Methods: PBMC were collected from 63 patients admitted to the intensive care unit (ICU) and from 20 healthy controls. Patients were divided in 3 subgroups: with AKI, with sepsis and without AKI and with AKI and sepsis. After isolation by ficoll-gradient centrifugation cells were incubated in vitro with LPS 1 ng/mL, simvastatin (10(-8)M) and with LPS plus simvastatin for 24 h. TNF-alpha and IL-10 concentrations on cells surnatant were determined by ELISA.Results: Cells isolated from critically ill patients showed a decreased spontaneous production of TNF-alpha and IL-10 compared to healthy controls (6.7(0.2-12) vs 103(64-257) pg/mL and (20 (13-58) vs 315(105-510) pg/mL, respectively, p < 0.05). Under LPS-stimulus, IL-10 production remains lower in patients compared to healthy control (451 (176-850) vs 1150(874-1521) pg/mL,p < 0.05) but TNF-alpha production was higher (641 (609-841) vs 406 (201-841) pg/mL, p < 0.05). the simultaneous incubation with LPS and simvastatin caused decreased IL-10 production in cells from patients compared to control (337 (135-626) vs 540 (345-871) pg/mL, p < 0.05) and increased TNF-alpha release (711 (619-832) vs 324 (155-355) pg/mL, p < 0.05). Comparison between subgroups showed that the results observed in TNF-alpha and IL-10 production by PBMC from critically ill patients was independent of AKI occurrence.Conclusions: the PBMC treatment with simvastatin resulted in attenuation on pro-inflammatory cytokine spontaneous production that was no longer observed when these cells were submitted to a second inflammatory stimulus. Our study shows an imbalance between pro and anti-inflammatory cytokine production in PBMC from critically ill patients regardless the presence of AKI. (C) 2011 Elsevier B.V. All rights reserved.