Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments

Abstract

LC is an herbal remedy effectively reduced therapeutic dosage of glucocorticoid for systemic lupus erythematosus (SLE) patients in clinical trial (ISRCTN81818883). This translational research examined the impact of LC on biomarkers of endothelial injury in the enrolled subjects. Fifty seven patients with SLE were randomized to receive standard treatment without or with LC supplements. Blood samples were taken serially for quantification of endothelial progenitor cells (EPCs), circulating endothelial cells (CECs) and serological factors. The proportion of EPCs in the placebo group continued to increase during trial and was further elevated after withdrawal of standard treatment. The EPC ratio of LC group remained stationary during the entire observation period. The CEC ratio in placebo group exhibited an increasing trend whereas that in LC group declined. The ratio of apoptotic CECs had an increasing trend in both groups, to a lesser extent in LC group. After treatment, the levels of VEGF and IL-18 have a trend declined to a level lower in the LC group than the placebo group. No significant alteration was noted in serum levels of IFN-α, IL-1β and IL-6. The reduction of the steroid dosage by adding LC might be correlated with less extensive endothelial injury in SLE patients.

Figure 1. Representative data for flow cytometric analysis of EPC, CEC and apoptotic CEC.

(A) Dot plot shows the gating strategy used to exclude debris; (B) The EPCs were characterized as CD31⁺ VEGFR-2⁺ CD45^dim CD133⁺; (C) The CECs were defined as CD31^Bright VEGFR-2⁺ CD45⁻ CD133⁻; (D) AAD-7 staining was used for identification and quantification of apoptotic CECs.

Figure 2. Serial changes in the amounts of EPCs, CECs and apoptotic CECs.

(A) EPC; (B) CEC; (C) apoptotic CEC. The ratios of EPC, CEC and apoptotic CEC were calculated by comparing pretreatment amounts of these cell populations of each own subject. *p <0.05.

Figure 3. Serum levels of cytokines in SLE patients.

(A) VEGF; (B) IL-18; (C) IL-1β; (D) IL-6; E, IFN-α.