Evidence for Monocyte Reprogramming in a Long-Term Postsepsis Study.

UNLABELLED

This study sought to identify monocyte alterations from septic patients after hospital discharge by evaluating gene expression of inflammatory mediators and monocyte polarization markers. It was hypothesized that sepsis reprograms the inflammatory state of monocytes, causing effects that persist after hospital discharge and influencing patient outcomes.

DESIGN

The gene expression patterns of inflammatory receptors, M1 and M2 macrophage polarization markers, NLRP3 inflammasome components, and pro- and anti-inflammatory cytokines in monocytes were assessed.

PATIENTS

Thirty-four patients from the University of São Paulo Hospital, during the acute sepsis phase (phase A), immediately after ICU discharge (phase B), and 3 months (phase C), 6 months (phase D), 1 year (phase E), and 3 years (phase F) after discharge, were included. Patients that died during phases A and B were grouped separately, and the remaining patients were collectively termed the survivor group.

MEASUREMENTS AND MAIN RESULTS

The gene expression of toll-like receptor () and (inflammatory receptors), , adaptor molecule apoptosis-associated speck-like protein containing a CARD, and (NLRP3 inflammasome components), , and high-mobility group box 1 protein (proinflammatory cytokines), (anti-inflammatory cytokine), C-X-C motif chemokine ligand 10, C-X-C motif chemokine ligand 11, and (M1 inflammatory polarization markers), and C-C motif chemokine ligand 14, C-C motif chemokine ligand 22, transforming growth factor-beta (), , and peroxisome proliferator-activated receptor γ (M2 anti-inflammatory polarization and tissue repair markers) was upregulated in monocytes from phase A until phase E compared with the control group.

CONCLUSIONS

Sepsis reprograms the inflammatory state of monocytes, probably contributing to postsepsis syndrome development and mortality.