Granulocytic myeloid‐derived suppressor cells inversely correlate with plasma arginine and overall survival in critically ill patients

Summary Critically ill patients display a state of immunosuppression that has been attributed in part to decreased plasma arginine concentrations. However, we and other authors have failed to demonstrate a clinical benefit of L ‐arginine supplementation. We hypothesize that, in these critically ill patients, these low plasma arginine levels may be secondary to the presence of granulocytic myeloid‐derived suppressor cells ( gMDSC ), which express arginase known to convert arginine into nitric oxide ( NO) and citrulline. Indeed, in a series of 28 non‐surgical critically ill patients, we showed a dramatic increase in gMDSC compared to healthy subjects ( P  = 0·0002). A significant inverse correlation was observed between arginine levels and gMDSC ( P  = 0·01). As expected, gMDSC expressed arginase preferentially in these patients. Patients with high gMDSC levels on admission to the medical intensive care unit ( MICU ) presented an increased risk of death at day 7 after admission ( P  = 0·02). In contrast, neither plasma arginine levels, monocytic MDSC levels nor neutrophil levels were associated with overall survival at day 7. No relationship was found between body mass index ( BMI) or simplified acute physiology score (SAPS) score, sequential organ failure assessment (SOFA) score or gMDSC levels, eliminating a possible bias concerning the direct prognostic role of these cells. As gMDSC exert their immunosuppressive activity via multiple mechanisms [production of prostaglandin E 2 ( PGE 2 ), interleukin ( IL) ‐10, arginase, etc.], it may be more relevant to target these cells, rather than simply supplementing with L ‐arginine to improve immunosuppression and its clinical consequences observed in critically ill patients.