Sivelestat sodium hydrate treatment for refractory Kawasaki disease

Ebata, Ryota; Yasukawa, Kumi; Nagai, Kazue; Saito, Yuko; Higashi, Kouji; Homma, Jun; Takada, Nobuyuki; Takechi, Fumie; Saito, Naoki; Kobayashi, Hironobu; Okunushi, Kentaro; Hamada, Hiromichi; Kohno, Yoichi; Hanaoka, Hideki; Shimojo, Naoki

doi:10.1111/ped.13851

Cited by 6 publications

(7 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sivelestat, a selective neutrophil elastase inhibitor, prevented phorbol myristate acetate-induced acute lung injury [ 193 , 194 ], enhanced coronary blood flow, and ameliorated myocardial damage after myocardial arrest [ 195 ]. Furthermore, it has shown its protective effect in neuromyelitis optica [ 196 ], refractory Kawasaki disease [ 197 ], knee osteoarthritis [ 198 ], steatohepatitis [ 199 ], and systemic inflammation such as burn [ 200 ]. BAY 85-8501, another selective and potent neutrophil elastase inhibitor, has been revealed to reduce pulmonary disease inflammation [ 201 ].…”

Section: Drug Developmentmentioning

confidence: 99%

Role of Neutrophils on the Ocular Surface

Mun

Hwang

Shin

2021

IJMS

View full text Add to dashboard Cite

The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.

show abstract

Section: Drug Developmentmentioning

confidence: 99%

Role of Neutrophils on the Ocular Surface

Mun

Hwang

Shin

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…The current study showed that anti-ApoA2 may act as an effective therapeutic agent for treating patients with KD. Antibody based drugs, such as infliximab (an anti-human tumor necrosis factor (TNF)-α monoclonal antibody [ 23 , 24 ]), cytokine antagonists (anakinra, interleukin 1 receptor antagonist, IL-1RA [ 25 ]), and immunosuppressants (e.g., mizoribin [ 20 ] and sivelestat [ 26 ]) have recently been suggested as therapeutic agents for patients with IVIg-resistant KD. As the suppression of TNF-α and IL-1RA diminishes the host response to infections, concerns have been raised regarding the safety of administering infliximab to patients receiving live viral vaccines.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease

et al. 2022

View full text Add to dashboard Cite

Background Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, “VasSF,” based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj). Apolipoprotein A-2 (ApoA2) has been identified as one of VasSF’s target molecules. Methods Here, we tested the potential of anti-apolipoprotein A-2 antibodies (anti-ApoA2) as a new therapeutic drug against KD by examining its effect on a mouse model, in which KD was induced via Candida albicans water-soluble fraction (CAWS). CAWS (2 mg/mouse) was injected intraperitoneally into C57BL/6NCrSlc mice for five consecutive days. The incidence and histological severity of vasculitis in CAWS-induced coronary arteritis in mice administered anti-ApoA2 was examined. The following experimental groups were tested: solvent (only PBS (−) injection); anti-ApoA2 antibodies at dosages of 0.05 mg, 0.1 mg, and 0.5 mg/kg/day; human IgG at 0.1 mg/kg/day. Results The group treated with anti-ApoA2 0.5 mg/kg/day showed a lower incidence of panvasculitis induced by CAWS, less inflammation of the coronary arteries and aortic roots, and lower levels of serum IL-6, M-CSF, and MIP-1α and 32 cytokines/chemokines compared with those in the solvent group. Conclusions The anti-ApoA2 treatment suppressed the development of coronary arteritis in an animal KD model and anti-ApoA2 shows potential as an effective therapeutic candidate for the treatment of KD vasculitis. The use of specific antibodies that display higher vasculitis-suppressing effects, such as anti-ApoA2, may attenuate KD as well as other infectious diseases, with less severe adverse side effects than treatment with IVIg.

show abstract

“…Intravenous immunoglobulin combined with oral aspirin is recognized as Classification I and Evidence levels A, 7 however, the precise mechanism is not clear. Although our knowledge on the efficacy of the NE inhibitor SSH is limited, the results of clinical studies in real‐world settings have been reported 10,11 . Our objective in this reverse translational study was to investigate the effectiveness of SSH by conducting basic studies on the pharmacology of SSH in mice with CAWS‐induced vasculitis.…”

Section: Discussionmentioning

confidence: 99%

“…Sivelestat sodium hydrate is cheaper and is considered more selective for NE than UTI. 10 Ebata et al 11 have also described the importance of combination treatment with IVIG and SSH for initial IVIG nonresponders; they reported that 62.2% of the non-responders responded to this treatment, with defervescence within 48 h, and the incidence of coronary aneurysm was restricted to 2.2%. These outcomes were superior to those of additional treatment with IVIG alone (10.0%-33.3%).…”

mentioning

confidence: 99%

Sivelestat's effect on Candida albicans water‐soluble fraction‐induced vasculitis

Yoshida¹,

Banno‐Terada²,

Takada³

et al. 2022

Pediatrics International

View full text Add to dashboard Cite

Background We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water‐soluble fraction‐induced vasculitis. Methods Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water‐soluble fraction‐induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM‐1) positive areas, ICAM‐1 and tumor necrosis factor‐α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood. Results The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH‐treated mice. The NE‐ and ICAM‐1‐positive regions, and the mRNA expression of ICAM‐1 and tumor necrosis factor‐α were lower in the SSH‐treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH‐treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH‐treated mice. Conclusions Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE‐inhibitory effect, SSH sites of action may also include monocytes.

show abstract

Sivelestat sodium hydrate treatment for refractory Kawasaki disease

Cited by 6 publications

References 45 publications

Role of Neutrophils on the Ocular Surface

Role of Neutrophils on the Ocular Surface

Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease

Sivelestat's effect on Candida albicans water‐soluble fraction‐induced vasculitis

Contact Info

Product

Resources

About