Myeloid-Derived Suppressor Cells in Patients With Acute Pancreatitis With Increased Inhibitory Function

Abstract

Acute pancreatitis (AP) is pancreatic or systemic inflammation without or with motion organ dysfunction. Severe acute pancreatitis (SAP) is the main cause of death for patients with AP. A pro-/anti-inflammatory imbalance is considered the key regulation of disease severity. However, the real mechanism of SAP remains unclear. This study aimed to identify the frequency and specific roll of myeloid-derived suppressor cell (MDSC) in AP. We evaluated MDSC frequency and disease severity by analyzing MDSCs in the peripheral blood of healthy controls (HCs) and patients with mild acute pancreatitis (MAP) and SAP by flow cytometry. We also compared the frequency and inhibitory ability of MDSCs from HCs and SAP, and finally detected the reason for the difference in inhibitory ability. AP was marked by expansion of MDSCs as well as its subsets, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). The proportion of MDSC in the peripheral blood mononuclear cells of patients with AP was increased and positively correlated with AP severity. The frequency of MDSC was decreased after treatment compared with pre-treatment. CD3+ T cells were remarkably inhibited by MDSC derived from the patients with SAP. In the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), the MDSCs from patients with SAP increased. These findings demonstrated that MDSCs expanded in the peripheral blood in patients with AP, especially in those with SAP. Moreover, the inhibitory ability of MDSCs was increased in the patients with SAP compared with that in the HCs. The enhanced suppressive function was possibly caused by an overexpression of Arg-1 and ROS.

Keywords: MDSC; ROS; acute pancreatitis; arginase-1; immunosuppression.