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2015 ; 180
(2
): 280-8
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Granulocytic myeloid-derived suppressor cells inversely correlate with plasma
arginine and overall survival in critically ill patients
#MMPMID25476957
Gey A
; Tadie JM
; Caumont-Prim A
; Hauw-Berlemont C
; Cynober L
; Fagon JY
; Terme M
; Diehl JL
; Delclaux C
; Tartour E
Clin Exp Immunol
2015[May]; 180
(2
): 280-8
PMID25476957
show ga
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
E2 (PGE2 ), 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.