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The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
Changing cytokine patterns in systemic lupus: a prospective longitudinal study
1Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Lin-kou and Chang Gung University College of Medicine, Tao-yuan, Taiwan. b890121@adm.cgmh.org.tw
Insights
Lupus patients
Area of Science:
- Immunology
- Systemic Lupus Erythematosus (SLE)
- Cytokine Signaling
Background:
- Monocytes in lupus patients exhibit distinct C-reactive protein (CRP)-inducing cytokine patterns (interleukin-6, IL-1beta, tumor necrosis factor-alpha) when stimulated by immune complexes (ICs) or lipopolysaccharide (LPS).
- Previous research established these differential cytokine secretion patterns in lupus monocytes.
Purpose of the Study:
- To investigate if peripheral blood mononuclear cell (PBMC) cytokine patterns in lupus patients shift over time.
- To determine if corticosteroid or hydroxychloroquine treatment influences these cytokine patterns.
- To analyze the relationship between cytokine patterns and disease markers.
Main Methods:
- PBMCs were collected from lupus patients at multiple time points (0, 1, 3, 6 months post-diagnosis).
- Cells were stimulated with either ICs or LPS.
- mRNA expression of IL-6, IL-1beta, and TNF-alpha was quantified using polymerase chain reaction.
- Patients' samples were categorized into IC-pattern or LPS-pattern based on cytokine response.
Main Results:
- IC-pattern PBMCs showed significantly higher mRNA expression of IL-6 and IL-1beta compared to LPS-pattern PBMCs.
- Serum CRP levels were significantly higher in the IC-pattern group.
- Serum CRP levels correlated positively with C3c and C4, and inversely with anti-double stranded DNA (anti-dsDNA) antibodies.
- Circulating ICs correlated positively with anti-dsDNA and inversely with C4.
Conclusions:
- Cytokine patterns in lupus patients can change dynamically, either spontaneously or in response to medication.
- Existing circulating ICs do not predetermine a patient's cytokine pattern.
- CRP levels are linked to the consumption of anti-dsDNA, indicating disease activity.
Background/Purpose:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
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