Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis

Abstract

SUMMARYIn this study, we measured the mRNA levels of adrenomedullin (AM), C-type natriuretic peptide, vascular endothelial growth factor, interleukin-1b (IL-1b ) and interleukin-6 (IL-6) in peripheral blood mononuclear cells (PBMC) of 34 patients with lupus nephritis (LN) (15 active and 19 inactive) and 30 healthy volunteers. mRNA levels were measured using a real-time quantitative PCR method. Compared with healthy volunteers, IL-6 mRNA levels were elevated in LN patients (P , 0´005), while AM mRNA levels were decreased (P , 0´05). Also, IL-6 mRNA levels were higher and AM mRNA levels lower in active LN patients compared with inactive LN patients. In addition, IL-6 mRNA levels positively correlated and AM mRNA levels negatively correlated with SLE disease activity index and laboratory findings, such as blood urea nitrogen, serum creatinine, 50% haemolytic unit of complement and urinary excretion of protein over 24 h. Furthermore, IL-6 mRNA levels were negatively correlated with AM mRNA levels within the same LN patients. With regard to pathological findings, our results showed that IL-6 mRNA levels were higher, and AM mRNA levels significantly lower in patients with a high activity index compared to those with a low activity index. Following treatment with prednisolone, IL-6 mRNA levels in active LN patients decreased and AM mRNA levels increased to levels comparable to those in inactive LN and healthy volunteers. In vitro studies further demonstrated that elevated IL-6 mRNA levels in active LN patient PBMC were suppressed by the addition of adrenomedullin. Our results suggest that an imbalance between IL-6 and AM levels may play an important role in the progression of SLE, and that the mRNA levels of these genes in PBMC may be used as a disease activity index for SLE.

Beneficial effect of magnolol on lupus nephritis in MRL/lpr mice by attenuating the NLRP3 inflammasome and NF-κB signaling pathway: A mechanistic analysis

“…U1-snRNP leads to overproduction of IL-1β, which has been observed to be significantly elevated in LN. This overproduction has additionally been promoted by dsDNA from human monocytes following innervation of the NLRP3 inflammasome in the presence of anti-dsDNA antibodies (30)(31)(32)(33)(34). The results of the present study were consistent with previous reports, demonstrating that NLRP3 inflammasome components were elevated in MRL/lpr mice compared with healthy controls and the vehicle treated group (Fig.…”

The role of vascular endothelial growth factor (VEGF) in renal pathophysiology

“…VEGF mRNA in PBMC of patients with SLE did not differ from those of controls [122]. VEGF plasma levels were higher in SLE patients than in controls, and SLE patients with renal failure had higher levels than those with normal renal function [123].…”

Biomarkers in systemic lupus erythematosus: II. Markers of disease activity

“…Lymphoblastoid cells isolated from lupus patients produce increased levels of IL‐6, and blocking of IL‐6 inhibited anti‐dsDNA production by lymphoblastoid cells in vitro (50). Increased basal and stimulated IL‐6 messenger RNA (mRNA) levels in PBMCs have been demonstrated in several studies (47, 51–54) and were shown to correlate with disease activity in the studies examining this correlation (47, 53). The frequency of IL‐6–secreting PBMCs was significantly higher in patients with SLE compared with healthy controls, independent of disease activity (55).…”