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[181-POS]: Association between pro-inflammatory cytokines and autophagy induction by sera from women with preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a clinical complication of pregnancy associated with high levels of inflammatory cytokines, leukocyte activation and oxidative stress. Autophagy, an intracellular catabolic process, which removes damaged organelles and cytoplasmic proteins seems to be able to maintain cellular homeostasis. Moreover, it also has a potent anti-inflammatory mechanism by destroying inflammasomes, an intracellular multi-protein structure required for processing and releasing bioactive Interleukin-1 beta (IL-1beta). The present study compared the ability of sera from pregnant women with or without preeclampsia to induce autophagy in peripheral blood mononuclear cells (PBMC), and the relationship between this activity and serum concentrations of uric acid, IL-1beta, IL-10 and TNF-alpha.

METHODS: PBMC from 20 healthy non-pregnant women were incubated with sera from 45 pregnant women, being 23 normotensive (NT) and 22 with PE in the presence or absence of rapamycin, an autophagy inducer. After 48h, the cells were assayed for p62, a cytoplasmic protein associated with autophagy inhibition. Sera from both groups of pregnant women were tested for IL-1beta, IL-10 and TNF-alpha by enzyme-linked immunosorbent assay.

RESULTS: Autophagy was induced to a greater extent by sera from women with PE than by NT pregnant women. The relationship between inflammatory cytokines in sera of preeclamptic pregnant women showed association between autophagy induction (decrease in cytoplasmic p62) and higher concentrations of IL-1beta (r= -0.4949; p=0.0192), and TNF-alpha (r=- 0.5302; p=0.0111). This relationship was absent in sera from NT women. There was no association between IL-10 or uric acid levels and autophagy both in preeclamptic and NT group.

CONCLUSIONS: Association between autophagy induction and higher levels of inflammatory cytokines in sera from patients with preeclampsia suggests that the enhanced pro-inflammatory state characteristic of preeclampsia may result in the up-regulation of autophagy induction in these women. Financial support: Fapesp 2014/00693-9.

DISCLOSURES: M.L. Matias: None. M.T. Peracoli: None. T.T. Kanninen: None. G. Sisti: None. M. Romao: None. I.C. Weel: None. J.C. Peracoli: None. A.M. Bongiovanni: None. S.S. Witkin: None.

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