Background and Aims

Sepsis outcome is determined by a balance between inflammation and immune suppression. We aimed to evaluate monocytes polarization and reprogramming during these processes.

Methods

We analyzed 75 patients with suspected/confirmed sepsis and 70 controls by analysis of CD14 and CD16 expression in blood monocytes (n=50 patients with procalcitonin level >0.5 ng/mL) and HLA-DR (n=25 patients with positive blood culture) using fluorescent labeled monoclonal antibodies and BD FACS CANTO II. Complete blood cell count, procalcitonin and C-reactive protein were evaluated.

Results

Intermediate monocytes CD14++CD16+ increased in high-procalcitonin patients compared to controls (p<0,001), while classical monocytes CD14++CD16- were reduced (p<0,001). Sepsis was confirmed by positive blood culture and clinical manifestations in 44% of these patients, while 56% showed strong inflammatory state confirmed by laboratory biomarkers. The latter subgroup showed a significant increase in intermediate monocytes and decrease in classical monocytes. Three-four days following the diagnosis of sepsis, HLA-DR expression in all monocyte subsets was lower (94,3%) compared to controls (99,4%) (p<0,05). Septic patients with the worst conditions showed higher incidence of secondary infections, long-time hospitalization and lower HLA-DR+ monocytes compared to septic patients with better outcome (88,4% and 98,6%, respectively) (p=0,05).

Conclusions

The dynamic nature of sepsis correlates with monocytes functional polarization and reprogramming from a pro-inflammatory CD14++CD16+ phenotype in non-septic/high-procalcitonin patients to a decrease of HLA-DR surface expression in patients with confirmed sepsis, which makes it a marker of immune paralysis and sepsis outcome.

Analysis of monocytes plasticity opens to new mechanisms responsible for pro/anti-inflammatory responses during sepsis, and new immunotherapies.