Higher levels ofgrp78and lower levels oftlr4anticipate a positive evolution of sepsis and patient survival

Abstract

In sepsis caused by Gram-negative bacteria, modulation of Toll-like receptor 4 (TLR4) activity by modulators such as glucose-regulated protein 78 kDa (GRP78), is believed to shift the equilibrium between pro- and anti-inflammatory downstream signaling cascade. We measured daily mRNA tlr4 and grp78 expression levels in peripheral blood of a cohort of septic patients, upon intensive care admission, and modeled these mRNA values based on a sine damping function. We obtained negative correlations between tlr4 and grp78 mRNA in the survivor group. In contrast, such relation is lost in the deceased patients. Loss of homeostasis predicted by our model within the initial 5 days of hospitalization was confirmed by death of those patients up to 28 days later. Measuring the correlation patterns of the expression of these two genes serves as a robust means to gauge sepsis progression, requiring only three points of measurement on the first day of hospitalization.