Levels of myeloid-derived suppressor cell-like cells in early sepsis: a comparative study with non-septic patients

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with immunosuppressive functions. While early expansion of MDSCs may be protective in various pathological states, their accumulation and role might differ in sepsis. This study aimed to compare the differences in circulating myeloid cells with MDSC phenotypes and their subsets between septic and non-septic patients in the early stage.

This was a prospective, single-center, observational cohort study. Critically ill patients were enrolled and divided into sepsis and non-sepsis groups. Flow cytometry was used to determine the percentages of peripheral blood CD11b⁺CD33⁺HLA-DR^-/low cells (herein referred to as MDSC-like cells) and their subsets (M-MDSC-like and PMN-MDSC-like cells). Levels of arginase-1 (ARG-1) and inducible nitric oxide synthase (iNOS) were measured. Clinical data were collected. All patients were followed for 28 days to record mortality.

Sixty patients were enrolled (sepsis group: n=38; non-sepsis group: n=22). No significant differences were found in gender, age, APACHE II score, ICU length of stay, or 28-day mortality between the two groups. However, the Charlson Comorbidity Index (CCI) was higher in the sepsis group (P = 0.005). Compared to the non-sepsis group, septic patients had significantly lower percentages of total MDSC-like cells and M-MDSC-like cells (P = 0.006; P = 0.003), while PMN-MDSC-like cells showed no difference. ARG-1 levels were higher in the sepsis group (P = 0.030). Furthermore, the sepsis group exhibited significantly elevated levels of IL-6, CRP, PCT, and SOFA scores (P<0.05), lower lymphocyte counts (P = 0.017), and more pronounced coagulation abnormalities, hypoalbuminemia, and increased cardiac/renal markers. Within the sepsis group, non-survivors had a significantly higher percentage of PMN-MDSC-like cells than survivors (P = 0.012).

In the early stage, septic patients exhibit a distinct response profile of myeloid cells with MDSC phenotypes compared to non-septic patients, characterized by attenuated expansion of total MDSC-like cells and M-MDSC-like cells but enhanced ARG-1 expression, alongside more severe inflammation, organ dysfunction, and lymphopenia. An elevated percentage of PMN-MDSC-like cells is associated with poor prognosis in sepsis.