IL-1 family cytokines and soluble receptors in systemic lupus erythematosus

Italiani, Paola; Manca, Maria Laura; Angelotti, Francesca; Melillo, Daniela; Pratesi, Federico; Puxeddu, Ilaria; Boraschi, Diana; Migliorini, Paola

doi:10.1186/s13075-018-1525-z

Cited by 51 publications

(48 citation statements)

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“…Results for ALS, SLE, and IgG4-related disease (RD) are from references [28, 29, 31–33] n.t. not tested…”

Section: Discussionmentioning

confidence: 99%

“…Measurable concentrations of IL-18 are detectable in sera of normal subjects, yet are increased in many pathological conditions [26, 27]. In pathological conditions in which both IL-18 and IL-18BP were measured, such as amyotrophic lateral sclerosis (ALS), systemic lupus erythematosus (SLE), and IgG4-related disease, the higher levels of circulating IL-18 are paralleled by increased circulating IL-18BP, most likely as an attempt to counteract the excess of IL-18 [28–33]. Similar to IL-1, IL-18 in AD appears to be a sign of increased inflammation, with higher levels of circulating IL-18 in AD patients, accumulation of IL-18 mRNA and protein in the AD brain and CSF, and increased production of IL-18 by AD monocytes [34–36].…”

Section: Introductionmentioning

confidence: 99%

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Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression?

Italiani

Puxeddu

Napoletano

et al. 2018

J Neuroinflammation

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112

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BackgroundAlthough the mechanisms underlying AD neurodegeneration are not fully understood, it is now recognised that inflammation could play a crucial role in the initiation and progression of AD neurodegeneration. A neuro-inflammatory network, based on the anomalous activation of microglial cells, includes the production of a number of inflammatory cytokines both locally and systemically. These may serve as diagnostic markers or therapeutic targets for AD neurodegeneration.MethodsWe have measured the levels of the inflammation-related cytokines and receptors of the IL-1 family in serum of subjects with AD, compared to mild cognitive impairment (MCI), subjective memory complaints (SMC), and normal healthy subjects (NHS). Using a custom-made multiplex ELISA array, we examined ten factors of the IL-1 family, the inflammation-related cytokines IL-1α, IL-1β, IL-18, and IL-33, the natural inhibitors IL-1Ra and IL-18BP, and the soluble receptors sIL-1R1, sIL-1R2, sIL-1R3, and sIL-1R4.ResultsThe inflammatory cytokines IL-1α and IL-1β, their antagonist IL-1Ra, and their soluble receptor sIL-1R1 were increased in AD. The decoy IL-1 receptor sIL-1R2 was only increased in MCI. IL-33 and its soluble receptor sIL-1R4 were also significantly higher in AD. The soluble form of the accessory receptor for both IL-1 and IL-33 receptor complexes, sIL-1R3, was increased in SMC and even more in AD. Total IL-18 levels were unchanged, whereas the inhibitor IL-18BP was significantly reduced in MCI and SMC, and highly increased in AD. The levels of free IL-18 were significantly higher in MCI.ConclusionsAD is characterised by a significant alteration in the circulating levels of the cytokines and receptors of the IL-1 family. The elevation of sIL-1R4 in AD is in agreement with findings in other diseases and can be considered a marker of ongoing inflammation. Increased levels of IL-1Ra, sIL-1R1, sIL-1R4, and IL-18BP distinguished AD from MCI and SMC, and from other inflammatory diseases. Importantly, sIL-1R1, sIL-1R3, sIL-1R4, and IL-18BP negatively correlated with cognitive impairment. A significant elevation of circulating sIL-1R2 and free IL-18, not present in SMC, is characteristic of MCI and disappears in AD, making them additional interesting markers for evaluating progression from MCI to AD.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1376-1) contains supplementary material, which is available to authorized users.

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“…Results for ALS, SLE, and IgG4-related disease (RD) are from references [28, 29, 31–33] n.t. not tested…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression?

Italiani

Puxeddu

Napoletano

et al. 2018

J Neuroinflammation

Self Cite

112

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“…In fact, monocytes play a fundamental role in the production of proinflammatory cytokines present in the peritoneal cavity and plasma from SLE-induced mice [54]. IFN-γ and TNFα [28] contribute to the great influx of CD4 T cells towards the peritoneal cavity in the first months after induction [55], whereas IL-1 has been considered a biomarker of disease activity or organ involvement in humans [56] [57].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in our model, the percentage of Treg cells in the blood was negatively correlated with TNFα and positively correlated with TGF β1 ; no correlation between Treg cells and IL-2 and IL-10 was observed. Thus, higher titers of TNFα [57] may play an important role in SLE development and could be responsible for an increased proinflammatory response especially in active disease [57] [75]. TGF β1 promotes the development of peripheral Treg cells, and curiously, IL-2, produced by activated T cells [72], may regulate Treg proliferation that contributes to homeostasis and maintenance of Treg suppressive capacity [65], which suggests a negative feedback.…”

Section: Discussionmentioning

confidence: 99%

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

et al. 2019

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Background: Adaptive immune cells, including CD4 + CD69 + and CD4 + CD25 + FoxP3 + regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4 + CD25 + FoxP3 + Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4 + CD69 + and CD4 + CD25 + FoxP3 + T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4 + CD69 + T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4 + CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFβ1 (p = 0.038). Conclusion: Increased numbers of CD4 + CD69 + T cells and reduced numbers of CD4 + CD25 + FoxP3 + Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.

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“…On the other hand, at least two studies reported different results. Italiani et al [29] conducted a study on IL-1 family molecules and SLE, and reported that IL-33 was significantly lower in SLE ( p = 0.002), whereas soluble interleukin 1 receptor 4 (sIL-1R4), its natural inhibitor, was significantly higher ( p < 0.0001). Moreover, they found no correlation between proteinuria and IL-33.…”

Section: Autoimmune Disordersmentioning

confidence: 99%

IL-33/IL-31 Axis in Immune-Mediated and Allergic Diseases

Murdaca

Greco

Tonacci

et al. 2019

IJMS

112

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Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet’s disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine—it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions. To date, several researchers have investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed to understand the future applications of these molecules as novel therapeutic agents. This paper aims to give the readers a complete and updated review of IL-31 and IL-33 involvement among the most common autoimmune and allergic disorders.

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IL-1 family cytokines and soluble receptors in systemic lupus erythematosus

Cited by 51 publications

References 46 publications

Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression?

Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression?

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

IL-33/IL-31 Axis in Immune-Mediated and Allergic Diseases

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