Changes Of M1 And M2-like Monocyte Subsets And The Underlying Mechanisms In Patients With Acute Pancreatitis

Background:Acute pancreatitis(AP)is the acute inflammatory disease of the pancreas.The mild acute pancreatitis(MAP)and severe acute pancreatitis(SAP)are two forms of AP,while the prognosis of them vary widely.The mortality due to the systemic inflammatory response syndrome(SIRS)and the multiple organ failure(MOF).At present,it is believed that the inflammation disorder exist during the pathogenesis of AP,the monocytes/macrophages are the main inflammatory cells participate in the inflammation disorder,and their activation is associated with the severity of AP.Monocytes/macrophages can be classically activated as M1 or alternatively activated as M2 cells.The M1 monocytes/macrophages can produce many types of pro-inflammatory cytokines,including interleukin(IL)-12,IL-1? and IL-6,help to clear out bacteria and tumor cells,and defense against infectious pathogens and tumors.The M2 macrophages are characterized by expressing anti-inflammatory cytokines(e.g.IL-10)and many other factors that regulate immune responses and tissue repair,but may promote tumor growth and metastasis.The polarized state of the nomocytes can be different as to different disease,and therefor,they can play different roles in different diseases.However,the polarized states and roles of monocytes immunity in the pathogenesis of MAP and SAP are poorly understood.Whether different polarization states of the monocytes and the cytokines they produced could aid in evaluating the severity and prognosis of MAP and SAP remain unclear.Aim:We aimed to study the phenotypic characterization,numbers,and function of different monocyte subsets and the levels of related serum cytokines in new-onset MAP and SAP patients.Furthermore,we explored the potential correlation between these cells and clinical parameters in patients with MAP and SAP.This study is aimed at evaluating the role of monocyte subsets in the pathogenesis of AP,and the mechanisms underlying perturbation of monocyte immunity.Methods:1.Peripheral blood from 24 patients with new-onset MAP and 13 healthy controls(HC)were examined for the frequencies of different subsets of monocytes by flow cytometry.The levels of serum IL-12 and IL-10 were measured using cytometric bead array(CBA).2.Peripheral blood from 21 patients with new-onset SAP,15 patients with new-onset MAP and 13 HC was examined for monocyte subsets by flow cytometry.The levels of serum IL-12 and IL-10 were measured using CBA.For all the patients participated in the experiments above,the APACHE II scores were caculated,and CRP levels were measured in individual subjects.Potential associations among the values of different measures were analyzed by the Spearman correlation test.Results:1.In comparison with that in HC,our data indicated significantly increased numbers of pro-inflammatory CD14+CD163-,CD 14+CD163-MAC3 87+,CD 14+CD163-IL-12+ Ml-like monocytes and reduced numbers of CD14+CD163+IL-10+ monocytes in the MAP patients.The levels of plasma CRP were positively correlated with the numbers of CD 14+CD 163-and CD14+CD163-MAC387+ M1-like monocytes in the MAP patients.In addition,we detected significantly increased numbers of CD14+CD163+CD115+ M2-like monocytes in MAP patients.Moreover,the numbers of CD 14+CD 163+CD115+monocytes were positively correlated with the levels of plasma CRP and the APACHE? scores simultaneously in MAP patients.The levels of plasma IL-12 and IL-10 were significantly increased in MAP patients,and the IL-10 levels were positively correlated with the APACHE ? scores.2.Compared to MAP and HC,we found increased numbers of CD14+CD163-,CD14+CD163-MAC387+ and CD14+CD163-IL-12+ Ml-like monocytes and CD115+,CD204+,and IL-10+ M2-like monocytes,along with higher plasma concentrations of IL-12 and IL-10 in SAP patients.The levels of plasma CRP were positively correlated with the numbers of CD14+CD163-and CD14+CD163-MAC387+M1-like monocytes and the plasma IL-12 levels in SAP patients,while the plasma IL-10 levels were positively correlated with the APACHE ? score.More importantly,we noticed positive associations between the number of the CD14+CD163+CD115+ subset and theAPACHE ? score as well as the plasma CRP concentration.The numbers of CD14+CD163-,MAC387+,and IL-12+ Ml-like monocytes and the CD115+,CD204+and IL-10+ M2-like monocytes were significantly decreased after treatment.The post-treatment plasma IL-12 and IL-10 levels in the patients were also significantly decreased as compared to levels before treatment.However,no significant differences were observed in the numbers of CD14+CD163+,CD206+ and MAC387+ M2-like monocytes compared with post-treatment numbers.Conclusions:1.Increased numbers of CD 14+CD163-,CD14+CD163-MAC3 87+ monocytes may contribute to the pathogenesis of MAP,and increased numbers of CD14+CD163+CD115+ monocytes may be a biomarker for evaluating the severity of MAP.2.The CD 14+CD 163+CD115+ M2-like monocyte count appears to be important factor in determining the severity and prognosis of SAP.Both the pro-and anti-inflammatory monocytes appear to participate in the pathogenesis of SAP.