Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Immune cell dynamics, cytokines, and extracellular vesicles in systemic inflammatory response syndrome (SIRS): a multiparametric analysis.

Abstract

BACKGROUND: The systemic inflammatory response syndrome (SIRS) is a complex and multifactorial life-threatening reaction triggered by trauma or infection (sepsis). Since the dynamics of immune cells, cytokines and novel markers such as circulating extracellular vesicles (EVs) remain incompletely elucidated, we aimed to provide a comprehensive multiparametric characterization of this severe response, to identify potential prognostic and therapeutic targets. METHODS: We conducted a multiparametric and sequential quantification of up to 25 immune cell circulating populations using next-generation flow cytometry, assessed plasma cytokine levels with Luminex technology, and the characterized and quantified EVs and their microRNA content. Peripheral blood samples were taken at 0, 24 and 72 h after SIRS onset from 25 patients with polytrauma-induced SIRS (PT group) and 25 developed SIRS from other origins, such as pulmonary or urinary infections (NP-denoting non-polytrauma group). Samples from 21 healthy donors (HD) were analysed as a control group. Statistical analyses were performed to compare experimental groups (PT, NP, HD) and to evaluate correlations between experimental findings and patients' outcomes for potential prognostic markers discovery. RESULTS: SIRS patients exhibited increased leukocyte counts driven by neutrophil mobilization combined with a reduction of dendritic cells and lymphocytes early after the SIRS. The PT group showed an increase in classical monocytes, myeloid-derived suppressor cells (MDSCs), and mesenchymal stromal cells compared to HD. These dynamics occurred alongside substantial chemokine release, including IL-8, G-CSF, CCL2 in both SIRS groups, MIF in PT and CCL4 in NP. Both SIRS groups experienced a pronounced cytokine storm with simultaneous release of both pro- and anti-inflammatory cytokines, and increased of plasma EV levels. Our findings suggest that elevated IL-8 concentrations and increased counts of circulating monocytes and MDSCs are associated with worse prognosis and may serve as valuable prognostic indicators in SIRS patients. CONCLUSIONS: Our study demonstrates the dynamic kinetics of multiple cell subsets, cytokines and EVs during SIRS, highlighting differences between SIRS initiated by polytrauma versus non-polytrauma events and identifying correlations between biological findings and patient outcomes.