Inhibition of IL-6 in the LCWE Mouse Model of Kawasaki Disease Inhibits Acute Phase Reactant Serum Amyloid A but Fails to Attenuate Vasculitis

Porritt, Rebecca A.; Huizar, Carol Chase; Dick, Edward J.; Kumar, Shyamesh; Escalona, Renee; Gómez, Alejandro Raúl Gratacós; Marek-Iannucci, Stefani; Rivas, Magali Noval; Patterson, Jean; Forsthuber, Thomas G.; Arditi, Moshe; Gorelik, Mark

doi:10.3389/fimmu.2021.630196

Cited by 9 publications

(7 citation statements)

References 57 publications

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“…IL-6, a pro-in ammatory cytokine, emerges as a central gure in the pathogenesis of KD, driving the immune response and vasculitis development. This aligns with prior research indicating elevated IL-6 levels in KD patients 8, 13,14 , which further validates the role of IL-6 in the in ammatory dynamics of KD.…”

Section: Discussionsupporting

confidence: 90%

Diagnostic Value of Interleukin-6 in Acute Kawasaki Disease: A Retrospective Study

Zhu,

Yuan,

Dai

et al. 2024

Preprint

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Purpose Kawasaki disease (KD) is an acute vasculitis affecting mainly young children and can cause serious coronary artery abnormalities. This study evaluated interleukin-6 (IL-6) as a biomarker for early KD diagnosis and treatment. Methods In a retrospective study, 275 children with acute KD were analyzed, alongside 109 children with other infectious diseases, to assess IL-6's diagnostic specificity. Patients were categorized by coronary artery lesions (CAL) presence and KD type. Results Of the KD patients (mean age 2.45 years), 84 had CAL. IL-6 levels were significantly higher in patients with CAL (223.56 pg/mL) versus without (95.18 pg/mL, p < 0.05) and compared to other infectious diseases (134.86 pg/mL vs. 33.38 pg/mL, p < 0.05). The optimal IL-6 cutoff for predicting CAL had a sensitivity and specificity of 0.6. IL-6 correlated with C-reactive protein (r = 0.404), but no difference was found between typical and incomplete KD. Conclusions Elevated IL-6 levels in acute KD, particularly with CAL, suggest its utility as a diagnostic biomarker. Further studies are needed to confirm IL-6's diagnostic role.

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Section: Discussionsupporting

confidence: 90%

Diagnostic Value of Interleukin-6 in Acute Kawasaki Disease: A Retrospective Study

Zhu,

Yuan,

Dai

et al. 2024

Preprint

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“…199,206,207 In contrast, administration of IL-6 blocking agents fails to inhibit the vascular damage response but does interfere with the induction of plasma acute phase reactants following injection of Lactobacillus casei wall extract. 208 Studies in humans also support the concept that IL-1 is an important cytokine mediator of Kawasaki disease. Genetic analysis of these patients shows a strong induction of IL-1 and its downstream effector pathways compared with controls implying its potential pathogenic role in the disease.…”

Section: Vascular Ecm Remodeling In Vasculitis Syndromesmentioning

confidence: 86%

Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence

Lin

Davis

2023

ATVB

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Because of structural and cellular differences (ie, degrees of matrix abundance and cross-linking, mural cell density, and adventitia), large and medium-sized vessels, in comparison to capillaries, react in a unique manner to stimuli that induce vascular disease. A stereotypical vascular injury response is ECM (extracellular matrix) remodeling that occurs particularly in larger vessels in response to injurious stimuli, such as elevated angiotensin II, hyperlipidemia, hyperglycemia, genetic deficiencies, inflammatory cell infiltration, or exposure to proinflammatory mediators. Even with substantial and prolonged vascular damage, large- and medium-sized arteries, persist, but become modified by (1) changes in vascular wall cellularity; (2) modifications in the differentiation status of endothelial cells, vascular smooth muscle cells, or adventitial stem cells (each can become activated); (3) infiltration of the vascular wall by various leukocyte types; (4) increased exposure to critical growth factors and proinflammatory mediators; and (5) marked changes in the vascular ECM, that remodels from a homeostatic, prodifferentiation ECM environment to matrices that instead promote tissue reparative responses. This latter ECM presents previously hidden matricryptic sites that bind integrins to signal vascular cells and infiltrating leukocytes (in coordination with other mediators) to proliferate, invade, secrete ECM-degrading proteinases, and deposit injury-induced matrices (predisposing to vessel wall fibrosis). In contrast, in response to similar stimuli, capillaries can undergo regression responses (rarefaction). In summary, we have described the molecular events controlling ECM remodeling in major vascular diseases as well as the differential responses of arteries versus capillaries to key mediators inducing vascular injury.

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“…The degree of alterations in IL‐6 levels in an animal model of KD vasculitis was similar to that observed in children with KD, which increased during the acute phase of KD, followed by a rapid reduction during the course of convalescence. IL‐6 fluctuates sensitively along with the inflammation development or inhibition by therapy in the acute phase of KD 13,35,36 . Therefore, changes in IL‐6 levels may be considered sensitive indicators of the extent of inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is significant variation in the identified independent risk factors for KD among children from different cities within the same region 7–11 . In addition, these prediction models tended to focus more on clinical features and indicators rather than on items associated with specific aspects of inflammation 11–15 . The diverse clinical perspectives on KD among researchers result in different factors being included in predictive models, and the varying number of cases can also lead to the development of distinct models.…”

Section: Introductionmentioning

confidence: 99%

Prediction of intravenous immunoglobulin retreatment in children with Kawasaki disease using models combining lymphocyte subset and cytokine profile in an East Asian cohort

Zhang,

Chen,

Bian

et al. 2024

Clin & Trans Imm

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ObjectivesFor children with Kawasaki disease (KD) at high risk of developing coronary artery lesions and requiring retreatment with intravenous immunoglobulin (IVIG), the availability of accurate prediction models remains limited because of inconsistent variables and unsatisfactory prediction results. We aimed to construct models to predict patient's probability of IVIG retreatment combining children's individual inflammatory characteristics.MethodsClinical manifestations and laboratory examinations of 266 children with KD were retrospectively analysed to build a development cohort data set (DC) and a validation cohort data set (VC). In the DC, binary logistic regression analyses were performed using R language. Nomograms and receiver operating curves were plotted. The concordance index (C index), net reclassification index, integrated discrimination improvement index and confusion matrix were applied to evaluate and validate the models.ResultsModels_5V and _9V were established. Both contained variables including the percentages of CD8+ T cells, CD4+ T cells, CD3+ T cells, levels of interleukin (IL)‐2R and CRP. Model_9V additionally included variables for IL‐6, TNF‐α, NT‐proBNP and sex, with a C index of 0.86 (95% CI 0.79–0.92). When model_9V was compared with model_5V, the NRI and IDI were 0.15 (95% CI 0.01–0.30, P < 0.01) and 0.07 (95% CI 0.02–0.12, P < 0.01). In the VC, the sensitivity, specificity and precision of model_9V were 1, 0.875 and 0.667, while those of model_5V were 0.833, 0.875 and 0.625.ConclusionModel_9V combined cytokine profiles and lymphocyte subsets with clinical characteristics and was superior to model_5V achieving satisfactory predictive power and providing a novel strategy early to identify patients who needed IVIG retreatment.

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Inhibition of IL-6 in the LCWE Mouse Model of Kawasaki Disease Inhibits Acute Phase Reactant Serum Amyloid A but Fails to Attenuate Vasculitis

Cited by 9 publications

References 57 publications

Diagnostic Value of Interleukin-6 in Acute Kawasaki Disease: A Retrospective Study

Diagnostic Value of Interleukin-6 in Acute Kawasaki Disease: A Retrospective Study

Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence

Prediction of intravenous immunoglobulin retreatment in children with Kawasaki disease using models combining lymphocyte subset and cytokine profile in an East Asian cohort

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