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Ferrari G.L.,Federal University of Sao Paulo | Redublo Quinto B.M.,Federal University of Sao Paulo | Batista de Souto Queiroz K.C.,Federal University of Sao Paulo | Iizuka I.J.,IAEH IEP Hospital Israelita Albert Einstein Institute Ensino e Pesquisa | And 11 more authors.

Purpose: To assess the in vitro effects of simvastatin on IL-10 and TNF-α 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 1ng/mL, simvastatin (10-8M) and with LPS plus simvastatin for 24h. TNF-α 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-α 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-α 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-α release (711 (619-832) vs 324 (155-355) pg/mL, p< 0.05). Comparison between subgroups showed that the results observed in TNF-α 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. © 2011 Elsevier Ltd. Source

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