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Functional benefits of corticosteroid and IVIG combination therapy in a coronary artery endothelial cell model of Kawasaki disease.

Abstract：

BACKGROUND:Kawasaki disease (KD) is the most common pediatric systemic vasculitides of unknown etiology. Recent clinical studies led to reappraisal of the usefulness of initial combination therapy of intravenous immunoglobulin (IVIG) plus a corticosteroid for patients with severe KD. However, the molecular mechanisms underlying the clinical benefits of that combination therapy remain unclear. Here, we used cultured human coronary artery endothelial cells (HCAECs), as a mimic of KD, to study the possible mechanisms responsible for the clinical benefits of adding a corticosteroid to standard IVIG therapy for patients with severe KD. METHODS:HCAECs were stimulated with TNF-α, IL-1α or IL-1β in the presence and absence of high-dose IgG and/or dexamethasone (DEX). The mRNA and protein concentrations for high-mobility group box-1 (HMGB1), IL-1α, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the culture supernatants were measured by quantitative PCR (qPCR) and ELISA, respectively. Apoptosis was evaluated by the caspase 3/7 activities. RESULTS:DEX, but not IgG, significantly inhibited apoptosis caused by inflammatory stimuli, resulting in effective reduction of HMGB1 and IL-1α protein release by HCAECs. As previously reported, DEX or IgG alone significantly suppressed TNF-α-induced production of IL-6 and G-CSF and mRNA expression, but induction of those cytokines by IL-1 s (IL-1α and IL-1β) was resistant to high-dose IgG. CONCLUSIONS:A corticosteroid can effectively inhibit the release of HMGB1 and IL-1α, which may be involved in IVIG resistance in KD. Since high-dose IgG does not have such beneficial anti-cytotoxic effects, adding a corticosteroid to standard IVIG therapy may help prevent the progression of IVIG resistance in KD.

journal_name

Pediatr Rheumatol Online J

journal_title

Pediatric rheumatology online journal

authors

Inoue T,Murakami S,Matsumoto K,Matsuda A

doi

10.1186/s12969-020-00461-6

subject

Has Abstract

pub_date

2020-10-06 00:00:00

pages

issue

issn

1546-0096

pii

10.1186/s12969-020-00461-6

journal_volume

pub_type

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Functional benefits of corticosteroid and IVIG combination therapy in a coronary artery endothelial cell model of Kawasaki disease.