Effects of anti-CD4 antibodies on the release of IL-6 and TNF-α in                 whole blood samples from patients with systemic lupus erythematosus

Brink, Ingo; Thiele, Bernhard; Burmester, Gerd‐Rüdiger; Trebeljahr, G; Emmrich, Frank; Hiepe, Falk

doi:10.1191/096120399678840882

Cited by 18 publications

(14 citation statements)

References 35 publications

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“…Brink et al (17) reported that even low doses of steroids inhibit cytokine synthesis in SLE patients. Similarly, in the present study, the effects of glucocorticoids on serum IL-9 levels and CD4 + IL-9 + T cells in SLE patients were investigated.…”

Section: Discussionmentioning

confidence: 99%

Increased interleukin-9 and CD4+IL-9+ T cells in patients with systemic lupus erythematosus

Ouyang

Shi

Liu

et al. 2013

Molecular Medicine Reports

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Abstract. Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin affecting all the organ systems. Apart from genetic and environmental factors, autoantibody and immune complex deposition as well as cytokine imbalances contribute to immune dysfunction. Interleukin-9 (IL-9) is a T cell-derived factor preferentially expressed by CD4 + T cells and it has been characterized in human and murine systems. IL-9 targets cells of the lymphoid, myeloid and mast cell lineages, and is likely to contribute to the development of allergic and autoimmune diseases such as asthma, arthritis, multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Nevertheless, until recently there have been no studies on its role in SLE in humans. In the present study, the mRNA and serum IL-9 levels in the peripheral blood of SLE patients and healthy controls were assessed using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Flow cytometry was used to analyze the percentages of CD4 + IL-9 + T cells in SLE patients. Moreover, differences between the groups and the effect of glucocorticoids were analyzed. The results showed that the plasma concentration and mRNA levels of IL-9 were significantly elevated in SLE patients compared with the healthy controls. The percentages of CD4 + IL-9 + T cells were also increased in SLE patients. In addition, serum IL-9 levels and the percentages of CD4 + IL-9 + T cells were correlated with the SLE disease activity index (SLEDAI). Additionally, the percentages of CD4 + IL-9 + T cells and serum IL-9 levels in 8 untreated active SLE patients were decreased at 1, 2 and 3 weeks after treatment with methylprednisolone. In conclusion, we provide evidence that IL-9 is increased in SLE patients. Moreover, it is described for the first time that high expression of IL-9 levels and the percentages of CD4 + IL-9 + T cells correlate with disease activity and severity. This suggests an important role of IL-9 in the pathogenesis of SLE.

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Section: Discussionmentioning

confidence: 99%

Increased interleukin-9 and CD4+IL-9+ T cells in patients with systemic lupus erythematosus

Ouyang

Shi

Liu

et al. 2013

Molecular Medicine Reports

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“…14 ± 18 They also seem to have effects on peroxisomal proliferating activating receptors (PPARs) and in particular the alpha subgroup of these receptors. 16,17,19 This action of statins results in a decrease in cytokine production by endothelial cells, eg interleukin- 6,20 and has been demonstrated to identify patients who bene®t from statin therapy in clinical trials in having co-associated falls in plasma CRP and cardiac events. 21 Whether all statins have similar actions, particularly in their effects on coagulation, is controversial.…”

Section: The Actions Of Lipid-lowering Drugsmentioning

confidence: 99%

Lipid-lowering drugs in lupus: an unexplored therapeutic intervention

Wierzbicki

2001

Lupus

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Lipid-lowering drugs have been shown to have profound actions beyond modulation of lipid profiles. Statins have been shown to reduce the levels of pro-inflammatory cytokines and markers of acute phase response including C-reactive protein and serum amyloid A. Fibrates have also shown to reduce interleukin-6 levels. Both groups of drugs seem to act through a peroxisomal proliferating activating receptor alpha mechanism to achieve these actions. In lupus, there is profound activation of cytokine production and the acute phase response and a markedly increased risk for the development of atherosclerosis. The role of lipid-lowering drugs in the management of both the acute and chronic sequelae of lupus needs to be explored.

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“…This information is important for an appreciation of our results, since all patients were receiving low to moderate doses of prednisone. Brink et al reported that even low doses of steroids can inhibit cytokine synthesis in patients with SLE 21. In another study, Swaak et al observed that patients with SLE taking prednisone at a dose of <15 mg/day showed a reduction in “ ex-viv o” production of IL-6 and TNF-α 22.…”

Section: Discussionmentioning

confidence: 99%

IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions

Carneiro

Fuzii

Kayser

et al. 2011

Clinics

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OBJECTIVE:To analyze cytokine gene expression in keratinocytes from patients with systemic lupus erythematosus (SLE).INTRODUCTION:Keratinocytes represent 95% of epidermal cells and can secrete several cytokines.METHODS:Keratinocytes were obtained by laser microdissection from 21 patients with SLE (10 discoid and 11 acute lesions) at involved and uninvolved sites. All patients were receiving a low/moderate prednisone dose and 18 were receiving chloroquine diphosphate. IL-2, IL-5, TNF-α and IFN-γ gene expression was evaluated by real-time PCR and expressed as the ratio (R) to a pool of skin samples from 12 healthy volunteers.RESULTS:Heterogeneity in cytokine gene expression was found among patients with SLE. Eighteen of 38 valid SLE samples (47%) presented overexpression (R>1) of at least one cytokine. Lesional skin samples tended to show higher cytokine expression than samples from uninvolved skin (p = 0.06). IL-5 and IFN-γ were the most commonly overexpressed cytokines. Samples with cytokine overexpression corresponded to more extensive and severe lesions. Prednisone dose did not differ between samples without cytokine overexpression (15.71±3.45 mg/day) and those with overexpressed cytokines (12.68±5.41 mg/day) (p = 0.216). Samples from all patients not receiving diphosphate chloroquine had at least one overexpressed cytokine.CONCLUSIONS:The heterogeneous keratinocyte cytokine gene expression reflects the complex immunological and inflammatory background in SLE. Patients with severe/extensive skin lesions showed a higher frequency of cytokine gene overexpression. Increased IFN-γ and IL-5 expression suggests that Th1 and Th2 cells are involved in SLE skin inflammation. The possibility that prednisone and antimalarial drugs may have contributed to low cytokine gene expression in some samples cannot be ruled out.

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Effects of anti-CD4 antibodies on the release of IL-6 and TNF-α in whole blood samples from patients with systemic lupus erythematosus

Cited by 18 publications

References 35 publications

Increased interleukin-9 and CD4+IL-9+ T cells in patients with systemic lupus erythematosus

Increased interleukin-9 and CD4+IL-9+ T cells in patients with systemic lupus erythematosus

Lipid-lowering drugs in lupus: an unexplored therapeutic intervention

IL-2, IL-5, TNF-α and IFN-γ mRNA expression in epidermal keratinocytes of systemic lupus erythematosus skin lesions

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