Relationship between vitamin D, IFN-γ, and E<sub>2</sub>levels in systemic lupus erythematosus

Kokić, Višnja; Kaliterna, Dušanka Martinović; Radić, Mislav; Perković, Dijana; Cvek, Maja; Čapkun, Vesna

doi:10.1177/0961203315605367

Cited by 23 publications

(23 citation statements)

References 28 publications

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“…However, interventional studies did not reach definite conclusions regarding the clinical efficacy of vitamin D treatment to treat SLE 43 . Our results are in agreement with another study, which showed that the levels of 25(OH)D were negatively associated with IFN‐γ levels 44 . It was demonstrated that 25(OH)D suppresses adaptive immunity, which leads to the inhibition of proliferation and differentiation of CD4 + Th0 cells into Th1 and Th17 cells.…”

Section: Discussionsupporting

confidence: 59%

“…43 Our results are in agreement with another study, which showed that the levels of 25(OH)D were negatively associated with IFN-γ levels. 44 It was demonstrated that 25(OH)D suppresses adaptive immunity, which leads to the inhibition of proliferation and differentiation of CD4 + Th0 cells into Th1 and Th17 cells. 25(OH)D also stimulates Th2 and Treg cells.…”

Section: Discussionmentioning

confidence: 99%

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Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

et al. 2017

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The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

et al. 2017

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“…In our study, there was no difference in IFNγ serum level between CLL and control subjects. Negative correlation between IFN-γ and 25-OH-D 3 was previously reported 44 ; however, we were unable to prove it. In addition, we showed only a tendency toward lowering IFN-γ after VD repletion.…”

Section: Discussioncontrasting

confidence: 55%

C–C motif ligand 11 reduction in CLL patients serum after vitamin D supplementation

et al. 2016

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Background: Vitamin D (VD) deficiency results in a worse prognosis in patients with chronic lymphocytic leukemia (CLL) and may affect the production of cytokines. Nonetheless, there is the lack of studies dealing with VD supplementation and its impact on chemokines in CLL patients. Aim: The primary endpoint of our interventional study was to evaluate the effect of cholecalciferol supplementation on serum chemokines levels in CLL patients. Materials and methods: Eighteen subjects with CLL were enrolled for the study. Six-month-long cholecalciferol supplementation was performed in CLL patients with serum 25-OH-D3 levels below 30 ng/ml. Cytokines levels were assessed at the beginning of the study and after 6 months. Baseline measurements of cytokines were compared to those in apparently healthy controls. Results: Increased levels of CCL2, CCL3, CCL4, CXCL8, CXCL10, TNFα, bFGF, G-CSF, and VEGF were found in CLL patients in comparison with the healthy controls. In the course of the VD supplementation a decrease in serum levels of chemokines CCL11, CCL3, and cytokine PDGF-BB was observed. The decrease of CCL11 was found in CLL patients on VD supplementation solely, whereas the decrease of CCL3 and PDGF-BB was observed in CLL subjects on both chemotherapy and VD supplementation. Conclusion: The VD supplementation may exert beneficial effect on chemokines levels in CLL patients with VD deficiency.

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“…Our data demonstrated that ex vivo production of IFN-γ is decreased in patients with active disease compared to patients with inactive disease. The results of our study are different from those of previous publications that have reported increased IFN-γ production or IFN-γ-related gene expression in SLE, because our study evaluated IFN-γ production after PHA stimulation in whole blood [ 6 , 7 , 20 ].…”

Section: Discussioncontrasting

confidence: 99%

“…Interferon gamma (IFN-γ) is predominantly produced by T cells and natural killer cells [ 3 ], and it plays a critical role in lupus [ 4 ]. Previous studies have shown that IFN-γ mRNA expression is increased in peripheral blood mononuclear cells (PBMC) [ 5 ], and that serum levels of IFN-γ are elevated in patients with SLE [ 6 , 7 ]. In addition, in vivo experiments in murine models of SLE have shown that elevations in IFN-γ mRNA levels are correlated with disease progression [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus

et al. 2017

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BackgroundLupus pathogenesis is closely associated with interferon gamma (IFN-γ), which plays a central role in innate and adaptive immunity. The aim of this study was to evaluate the ex vivo production of IFN-γ after stimulation of peripheral blood mononuclear cells with phytohemagglutinin (PHA) in patients with lupus, according to disease activity.MethodsThis study included 118 patients with lupus who had undergone IFN-γ-releasing assays (IGRAs) to screen for tuberculosis. Data on IFN-γ production in negative (nil) and positive (mitogen with PHA) controls were collected and analysed. The difference (mitogen minus nil) was used to calculate ex vivo IFN-γ production. Disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Poor hospitalisation outcome was defined as in-hospital mortality or intensive care unit admission. Associations among disease activity, poor hospitalisation outcome, and ex vivo IFN-γ production were assessed.ResultsThe level of ex vivo IFN-γ production was significantly lower in patients with active systemic lupus erythematosus (SLE) (n = 64) than in those with inactive SLE (n = 54) (median 0.92 vs. 11.06 IU/mL, p < 0.001). Ex vivo IFN-γ production was correlated with the SLEDAI-2 K (r = − 0.587, p < 0.001). Results of multivariate logistic regression analysis showed that ex vivo IFN-γ production ≤ 7.19 IU/mL was an independent predictor for discriminating active and inactive lupus. In addition, patients with ex vivo IFN-γ production ≤ 0.40 IU/mL had more frequent poor hospitalisation outcomes than those with ex vivo IFN-γ production > 0.40 (40.0% vs. 9.3%, p = 0.001). The proportion of indeterminate IGRA results was higher in patients with active lupus than in those with inactive lupus (45.3% vs. 0.0%, p < 0.001) because of decreased ex vivo IFN-γ production.ConclusionsEx vivo IFN-γ production is a useful biomarker for assessing disease activity and predicting poor clinical outcomes of SLE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1404-z) contains supplementary material, which is available to authorized users.

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Relationship between vitamin D, IFN-γ, and E₂levels in systemic lupus erythematosus

Cited by 23 publications

References 28 publications

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

C–C motif ligand 11 reduction in CLL patients serum after vitamin D supplementation

Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus

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Relationship between vitamin D, IFN-γ, and E2levels in systemic lupus erythematosus

Cited by 23 publications

References 28 publications

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

C–C motif ligand 11 reduction in CLL patients serum after vitamin D supplementation

Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus

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Relationship between vitamin D, IFN-γ, and E₂levels in systemic lupus erythematosus