| Background:As one of the most important innate immune cells, monocytes are characterized by its obvious heterogeneity and it could be divided into3subpopulations, the classical subset (CD14++CD16-), the intermediate subset (CD14++CD16+) and the non-classical subset (CD14+CD16++) according to CD16expression level on it. IL-1β and TNF-a play a critic role as the pro-inflammatory cytokines secreted by the non-classical subset. CD16+subgroup has more intensive pro-inflammatory function than CD16-subgroup, which proliferates distinctly in the most inflammatory diseases especially for autoimmune diseases, and consequently elevated level of IL-1β and TNF-a provides evidence of its important role in the autoimmune diseases course. Neuromyelitis optica (NMO) is typical autoimmune disease in central nervous system (CNS), and the activated monocytes are one of the earliest immune cells of arrival at inflammatory site in CNS. The pro-inflammatory cytokines, IL-1β and TNF-α, also participated in the NMO pathological process. However, it is unclear that how the three subsets of monocytes change in NMO and whether they would be influenced by glucocorticoids during conventional NMO treatment.Objective:To observe how the3subsets of monocytes (classical subset, intermediate subset and non-classical subgroup) change in NMO and explore its possible role in the onset of NMO. To provide theoretical basis of NMO target therapy in monocytes and its cytokines by investigating the influences of glucocorticoids pulse therapy on monocyte subgroups distribution.Methods:A total of20NMO patients in acute phase,15healthy controls and10 non-inflammatory neurological diseases (NIND) patients were reviewed. EDSS score was examined before and after glucocorticoids pulse therapy among NMO patients. The percentage of3monocyte subsets was tested by Flow Cytometer. The relative expression of IL-1β and TNF-α mRNA in monocytes was tested by Real-time fluorescent quantitative PCR (qRT-PCR) and the content of which in plasma and cerebrospinal fluid was tested by ELISA. Data analysis is executed by SPSS17.0for windows, using parameter comparison and correlative analysis.Results:Compared with the healthy controls, both the non-classical and intermediate subsets of monocytes in NMO patients proliferated distinctly, while the classical subset obviously decreased. After glucocorticoids pulse therapy, the total amount of monocytes in PBMC declined in NMO patients, the occurrence of non-classical subset obviously decreased, the percentage of intermediate subgroup had no obviously changes while the amount of typical subgroup increased distinctly. In NMO patients, EDSS score obviously improved after glucocorticoids pulse therapy compared with that before therapy. Before and after therapy, changes in both non-classical and classical subsets of monocytes were respectively positively correlated to EDSS scoring improvement, while changes in intermediate subset had no correlation with EDSS scoring improvement. Before glucocorticoids pulse therapy, the expression of IL-1β、TNF-α mRNA in monocytes and the level of IL-1β、TNF-α both in plasma and cerebrospinal fluid were elevated while decreased after therapy. Before therapy, the expression of IL-1βand TNF-α mRNA was positively correlated to the percentage of non-classical subset in NMO patients, while had no correlation to that of intermediate or classical subset. Both before and after therapy in NMO patients, the changes of plasma IL-1β and TNF-α were positively correlated to EDSS scoring improvement.Conclusions:1. There is an imbalance of CD16+/CD16-monocytes in NMO patients, which shows the elevated percentage of CD16+monocytes and the opposite changes in CD16-monocytes. 2. The non-classical subset of monocytes in acute phage of NMO patients may give rise to the disease via increasing the secretion of IL-1β、TNF-α.3. Glucocorticoids pulse therapy plays therapeutic role in NMO therapy by suppressing proliferation of non-classical subset of monocytes and correting imbalance of CD16+/CD16-monocytes. |
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