Pro-Inflammatory Cytokines are Elevated in Pregnant Women with Systemic Lupus Erythematosus in Association with the Activation of TLR4.

Abstract

Autoimmune systemic lupus erythematosus (SLE) is associated with inflammatory activity and frequently causes complications in pregnant women. The aim of the current study was to investigate the serum levels of chemokines and cytokines (CKs) in SLE women during pregnancy and to examine the activation of toll-like receptor 4 (TLR-4) signaling in the deregulation of chemokines and CKs. Blood samples from pregnant women with or without SLE were assayed for the levels of CKs (interleukin (IL)-1β, IL-6, IL-8, and IFN-α), chemokines (IP-10 and RANTES) with enzyme-linked immunosorbent assay (ELISA) and were examined for toll like receptor (TLR)-2, -4, -7, -8 and -9. Then the peripheral blood mononuclear cells (PBMCs) from the SLE or normal pregnant women were treated with lipopolysaccharide (LPS) and were assayed for the CKs promotion. It was demonstrated that there were higher serum concentrations of IL-1p, IL-8, IFN-t, and IP-10 (p < 0.05, p < 0.01 or p < 0.0001) in the SLE pregnant women than in the non-SLE pregnant women. Additionally, the TLR-4 at the mRNA level in the PBMCs was also significantly higher in the SLE pregnant women than in the non-SLE pregnant women (p < 0.05). Moreover, the upregulated IL-1β, IL-8, IFN-α or IP-10 was associated with the promoted TLR-4 level in PBMCs of those SLE patients. In addition, the PBMCs from the SLE pregnant women were more responsive to LPS stimulation. There was more promoted IL-1β, IL-8, or IFN-α in the PBMCs from the SLE pregnant women. High levels of pro-inflammatory CKs and chemokines were promoted during pregnancy in women with SLE, possibly increasing their risk for pregnancy complications. In addition, the TLR4 signaling might play an important role in such CKs promotion.