Role of interleukin-18 in the pathophysiology of allergic diseases

Sanders, Nathan L; Mishra, Anil

doi:10.1016/j.cytogfr.2016.07.001

Cited by 43 publications

(36 citation statements)

References 144 publications

(129 reference statements)

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“…These data indicate that eotaxin-1 may not be critical for intestinal eosinophil accumulation when IL-18 expression is locally induced. 17,27,38 These findings are consistent with earlier reports regarding the role for eotaxin-1 in regulating eosinophil homing to the gastrointestinal tract in health and diseases. 1,42,43 Similarly, eotaxin-2 was not found to be induced in Fabpi-IL-18 transgenic mice.…”

Section: Discussionsupporting

confidence: 92%

“…The current study provides a mechanistic understanding regarding a direct role of IL-18 in promoting eosinophilia in the intestine, and supports our previous findings that IL-18 overexpression promotes EoE. 17,27,38 Notably, several eosinophil-associated gastrointestinal disorders have co-existing peripheral blood eosinophilia. 44,45 These patients have induced levels of IL-18, and we show that IL-18 intestinal transgenic mice had both induced peripheral blood and intestinal eosinophil accumulation.…”

Section: Discussionsupporting

confidence: 88%

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Intestinal overexpression of IL‐18 promotes eosinophils‐mediated allergic disorders

et al. 2019

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Summary Baseline eosinophils reside in the gastrointestinal tract; however, in several allergic disorders, excessive eosinophils accumulate in the blood as well in the tissues. Recently, we showed in vitro that interleukin (IL)‐18 matures and transforms IL‐5‐generated eosinophils into the pathogenic eosinophils that are detected in human allergic diseases. To examine the role of local induction of IL‐18 in promoting eosinophil‐associated intestinal disorders, we generated enterocyte IL‐18‐overexpressing mice using the rat intestinal fatty acid‐binding promoter (Fabpi) and analysed tissue IL‐18 overexpression and eosinophilia by performing real‐time polymerase chain reaction, Enzyme‐Linked Immunosorbent Assay and anti‐major basic protein immunostaining. Herein we show that Fabpi‐IL‐18 mice display highly induced IL‐18 mRNA and protein in the jejunum. IL‐18 overexpression in enterocytes promotes marked increases of eosinophils in the blood and jejunum. Our analysis shows IL‐18 overexpression in the jejunum induces a specific population of CD101+ CD274+ tissue eosinophils. Additionally, we observed comparable tissue eosinophilia in IL‐13‐deficient‐Fabpi‐IL‐18 mice, and reduced numbers of tissue eosinophils in eotaxin‐deficient‐Fabpi‐IL‐18 and IL‐5‐deficient‐Fabpi‐IL‐18 mice compared with Fabpi‐IL‐18 transgenic mice. Notably, jejunum eosinophilia in IL‐5‐deficient‐Fabpi‐IL‐18 mice is significantly induced compared with wild‐type mice, which indicates the direct role of induced IL‐18 in the tissue accumulation of eosinophils and mast cells. Furthermore, we also found that overexpression of IL‐18 in the intestine promotes eosinophil‐associated peanut‐induced allergic responses in mice. Taken together, we provide direct in vivo evidence that induced expression of IL‐18 in the enterocytes promotes eotaxin‐1, IL‐5 and IL‐13 independent intestinal eosinophilia, which signifies the clinical relevance of induced IL‐18 in eosinophil‐associated gastrointestinal disorders (EGIDs) to food allergens.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Intestinal overexpression of IL‐18 promotes eosinophils‐mediated allergic disorders

et al. 2019

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“…IL-18 is a pro-inflammatory cytokine that induces IFN-γ production, which is closely related to the pathophysiologic mechanism of allergic respiratory disorders [28]. In the present study, we showed that free plasma IL-18 was elevated in pAR and sAR patients, sAR patients had a decreased IL-18BP/IL-18 ratio (9.7), and free IL-18 correlated well with free IL-18BP in the plasma of both pAR patients and sAR patients, indicating that the imbalance between IL-18 and IL-18BP is likely to be crucial to the development of AR as a molar excess of 10 of IL-18BP over IL-18 is required to decrease a pathological level of 400 pg/ml of IL-18 to a level of a HC subject (40 pg/ml) [11].…”

Section: Discussionmentioning

confidence: 99%

Altered expression of IL-18, IL-18 binding protein and IL-18 receptor in blood monocytes of patients with allergic rhinitis

Wang

et al. 2020

Preprint

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Background: Interleukin (IL)-18 is emerging as an attractive participant in allergic rhinitis (AR). However, correlation of IL-18 with IL-18 binding protein (BP) in plasma, and expression of IL-18, IL-18BP and IL-18 receptor (R) in AR blood monocytes remains obscure. Methods: We investigated IL-18, IL-18BP and IL-18R expression in monocytes by using flow cytometric analysis, murine AR model, and quantitative realtime PCR in the present study. Results: It was found that plasma IL-18 and IL-1β in AR patients was higher than those in healthy control subjects. Free (f)IL-18 had a high correlation with IL-18BP, IL-1β and TNF-α in AR plasma. Proportion of IL-18 + monocytes was increased, whereas IL-18BP + monocytes were decreased in blood of patients with AR. It was found that Platanus pollen allergen extract provoked the elevated expression of IL-18 and IL-18R in AR blood monocytes. Dermatophagoides pteronyssinus , Artemisia sieversiana wild and Platanus pollen allergen extracts enhanced IL-18R protein and mRNA expression in primary monocytes from AR patients. Moreover, numbers of macrophages and IL-18R + macrophages in nasal lavage fluid (NLF) were increased, and levels of IL-18 in both plasma and NLF were elevated in AR mice. Conclusions: IL-18 is likely to participate in the development of AR as a causative factor, therefore it could be a therapeutic target for AR.

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“…IL-18 is a potential pro-inflammatory cytokine. Although the involvement of IL-18 has been implicated in various diseases, especially autoimmune diseases, such as allergy and systemic lupus erythematosus 7 , 21 , only a few studies have demonstrated IL-18 regulation is involved in inflammatory myopathy 22 . We show that HIMF induces IL-18 expression in murine myoblasts through PDK1, which acts as a downstream effector in the PI3K/Akt/c-Jun signaling pathway and has been implicated in the regulation of neutrophil migration.…”

Section: Discussionmentioning

confidence: 99%

“…Under pathological conditions, angiogenesis stimulates vascular endothelial growth factor (VEGF) expression in the smooth muscle cell phenotype 6 . Interleukin-18 (IL-18) is a pro-inflammatory cytokine that belongs to the IL-1 family, and has been identified in autoimmune disorders 7 . High levels of serum IL-18 have been observed in patients with inflammatory myopathy 8 .…”

Section: Introductionmentioning

confidence: 99%

Hypoxia induced mitogenic factor (HIMF) triggers angiogenesis by increasing interleukin-18 production in myoblasts

Wang

Liu

et al. 2017

Sci Rep

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Inflammatory myopathy is a rare autoimmune muscle disorder. Treatment typically focuses on skeletal muscle weakness or inflammation within muscle, as well as complications of respiratory failure secondary to respiratory muscle weakness. Impaired respiratory muscle function contributes to increased dyspnea and reduced exercise capacity in pulmonary hypertension (PH), a debilitating condition that has few treatment options. The initiation and progression of PH is associated with inflammation and inflammatory cell recruitment and it is established that hypoxia-induced mitogenic factor (HIMF, also known as resistin-like molecule α), activates macrophages in PH. However, the relationship between HIMF and inflammatory myoblasts remains unclear. This study investigated the signaling pathway involved in interleukin-18 (IL-18) expression and its relationship with HIMF in cultured myoblasts. We found that HIMF increased IL-18 production in myoblasts and that secreted IL-18 promoted tube formation of the endothelial progenitor cells. We used the mouse xenograft model and the chick chorioallantoic membrane assay to further explore the role of HIMF in inflammatory myoblasts and angiogenesis in vivo. Thus, our study focused on the mechanism by which HIMF mediates IL-18 expression in myoblasts through angiogenesis in vitro and in vivo. Our findings provide an insight into HIMF functioning in inflammatory myoblasts.

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Role of interleukin-18 in the pathophysiology of allergic diseases

Cited by 43 publications

References 144 publications

Intestinal overexpression of IL‐18 promotes eosinophils‐mediated allergic disorders

Intestinal overexpression of IL‐18 promotes eosinophils‐mediated allergic disorders

Altered expression of IL-18, IL-18 binding protein and IL-18 receptor in blood monocytes of patients with allergic rhinitis

Hypoxia induced mitogenic factor (HIMF) triggers angiogenesis by increasing interleukin-18 production in myoblasts

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