Changing Cytokine Patterns in Systemic Lupus: A Prospective Longitudinal Study

Abstract

We have previously reported that lupus monocytes display distinctively differing patterns of C-reactive protein (CRP)-inducing cytokine interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF)-alpha secretion when stimulated with either immune complexes (ICs) or lipopolysaccharide (LPS). In this study, we investigated whether the cytokine patterns of peripheral blood mononuclear cells (PBMCs) isolated from lupus patients acquired an IC or LPS pattern, either over time, or following corticosteroid or hydroxychloroquine use. PBMCs from lupus patients were obtained at 0, 1, 3, and 6 months post diagnosis and stimulated with ICs or LPS. Cells were obtained for polymerase chain reaction to determine the IL-6, IL-1beta, and TNF-alpha mRNA expression, and were assigned as having acquired either an IC or an LPS pattern. Upon stimulation, the mRNA expression levels of the IL-6 and IL-1beta were significantly higher in IC-pattern PBMCs than in LPS-pattern PBMCs (p= 0.021 and 0.028, respectively). Consistent with this, serum CRP levels in the IC-pattern group were significantly higher than those in the LPS-pattern groups (p = 0.027). Total serum CRP levels were positively correlated with serum C3c and C4 concentrations, and inversely correlated with serum anti-double stranded DNA (anti-dsDNA) levels. Conversely, circulating ICs were positively correlated with serum anti-dsDNA levels and inversely correlated with serum C4 concentrations. Within the same individual, the CRP-inducing cytokine patterns can be changed, either naturally or after medication. Pre-existing serum circulating ICs are not predisposed to either IC or LPS cytokine patterns. Finally, CRP levels were correlated with anti-dsDNA consumption.