Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease

Hamada, Hiromichi; Suzuki, Hiroyuki; Abe, Jun; Suzuki, Yôichi; Suenaga, Tomohiro; Takeuchi, Takashi; Yoshikawa, Norishige; Shibuta, Shoichi; Miyawaki, Michiyo; Oishi, Ko; Yamaga, Hiroo; Aoyagi, Noriyuki; Iwahashi, Seiji; Miyashita, Ritsuko; Honda, Takafumi; Onouchi, Yoshihiro; Terai, Masaru; Hata, Akira

doi:10.1016/j.cyto.2012.08.006

Cited by 37 publications

(32 citation statements)

References 18 publications

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“…[164][165][166] Recently, Coombs-positive hemolytic anemia complicating IVIG administration has been reported, especially in individuals with AB blood type. [167][168][169] Aseptic meningitis can occur as a result of IVIG infusion, but it resolves quickly without neurological sequelae. 170 Clinical studies comparing the efficacy of different immune globulin products have been conflicting.…”

Section: Intravenous Immunoglobulinmentioning

confidence: 99%

“…In a separate report, the levels of soluble IL-6 and IL-2 receptors dropped to control levels by 7 days after initiation of cyclosporine. 169 Randomized trials are needed to determine whether calcineurin inhibitors such as cyclosporine or tacrolimus reduce the rate of coronary artery aneurysms; however, these small studies suggest that cyclosporine has few serious adverse events and is a well-tolerated option for treatment of highly refractory patients, although further study is needed.…”

Section: Cyclosporinementioning

confidence: 99%

See 1 more Smart Citation

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

2,870

4,124

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BACKGROUND:Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries. METHODS AND RESULTS:To revise the previous American Heart Association guidelines, a multidisciplinary writing group of experts was convened to review and appraise available evidence and practice-based opinion, as well as to provide updated recommendations for diagnosis, treatment of the acute illness, and long-term management. Although the cause remains unknown, discussion sections highlight new insights into the epidemiology, genetics, pathogenesis, pathology, natural history, and longterm outcomes. Prompt diagnosis is essential, and an updated algorithm defines supplemental information to be used to assist the diagnosis when classic clinical criteria are incomplete. Although intravenous immune globulin is the mainstay of initial treatment, the role for additional primary therapy in selected patients is discussed. Approximately 10% to 20% of patients do not respond to initial intravenous immune globulin, and recommendations for additional therapies are provided. Careful initial management of evolving coronary artery abnormalities is essential, necessitating an increased frequency of assessments and escalation of thromboprophylaxis. Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. Patients with aneurysms require life-long and uninterrupted cardiology follow-up. CONCLUSIONS:These recommendations provide updated and best evidence-based guidance to healthcare providers who diagnose and manage Kawasaki disease, but clinical decision making should be individualized to specific patient circumstances. K awasaki disease (KD) is an acute, self-limited febrile illness of unknown cause that predominantly affects children <5 years of age. When initially described, the potential for coronary artery complications was not appreciated. KD is now the most common cause of acquired heart disease in children in developed countries. In the absence of pathognomonic tests, the diagnosis continues to rest on the identification of principal clinical findings and the exclusion of other clinically similar entities with known causes. Timely initiation of treatment with intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery aneurysms defined from absolute luminal dimensions from 25% to ≈4%. Ongoing studies with additional therapies have not substantially reduced this residual risk. The long-term prognosis is determined by the initial and current level of coronary artery involvement. Certain subsets of patients are at risk for myocardial ischemia from coronary artery thrombosis and stenoses. Medical management of such patients hinges on judicious use of thromboprophylaxis and vigilance to identify evolving stenoses. Invasive revascul...

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Section: Intravenous Immunoglobulinmentioning

confidence: 99%

Section: Cyclosporinementioning

confidence: 99%

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

McCrindle¹,

Rowley²,

Newburger³

et al. 2017

Circulation

2,870

4,124

View full text Add to dashboard Cite

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“…Thus, blockade of extracellular cyclophilin-CD147 interactions may have a potential to reduce inflammation and infiltration of inflammatory cells into infected tissues. In fact, studies of serum inflammatory cytokine profiles demonstrated that treatment of acute systemic vasculitis (Kawasaki disease) with cyclosporine (a known cyclophilin inhibitor) resulted in downregulation of cyclophilin-induced pathways, including CD147-mediated inflammation (17). Therefore, specific targeting of extracellular cyclophilins may be a valid therapeutic strategy to inhibit CD147-dependent pathways.…”

Section: Targeting Extracellular Cyclophilins Ameliorates Disease Promentioning

confidence: 99%

Targeting Extracellular Cyclophilins Ameliorates Disease Progression in Experimental Biliary Atresia

Iordanskaia

Malešević

Fischer

et al. 2015

Mol Med

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Biliary atresia (BA) is a devastating liver disease of unknown etiology affecting children generally within the first 3 months of life. The disease is manifested by inflammation and subsequent obstruction of the extrahepatic bile ducts, fibrosis and liver failure. The mechanisms responsible for disease pathogenesis are not fully understood, but a number of factors controlled by the SMAD signaling pathway have been implicated. In this study, we investigated the role of a known proinflammatory factor, extracellular cyclophilin A (CypA), in the pathogenesis of biliary atresia using the rhesus rotavirus (RRV) murine model. We used a unique cyclosporine A derivative, MM284, which does not enter cells and therefore inactivates exclusively extracellular cyclophilins, as a potential treatment. We demonstrated that levels of CypA in plasma of RRV-infected mice were increased significantly, and that treatment of mice with MM284 prior to or one day after disease initiation by RRV infection significantly improved the status of mice with experimental BA: weight gain was restored, bilirubinuria was abrogated, liver infiltration by inflammatory cells was reduced and activation of the SMAD pathway and SMAD-controlled fibrosis mediators and tissue inhibitor of metalloproteinases (TIMP)-4 and matrix metalloproteinase (MMP)-7 was alleviated. Furthermore, treatment of human hepatic stellate cells with recombinant cyclophilin recapitulated SMAD2/3 activation, which was also suppressed by MM284 treatment. Our data provide the first evidence that extracellular cyclophilins activate the SMAD pathway and promote inflammation in experimental BA, and suggest that MM284 may be a promising therapeutic agent for treating BA and possibly other intrahepatic chronic disorders.

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“…Therefore, the binding of CSA to CyPA may inhibit AS. Previous studies of organ transplantation in rats have suggested that CSA is able to downregulate the expression of TNF-α (22–24). In the present study, the relative expression levels of IL-6 were slightly reduced in the CSA intervention groups as compared with the groups that did not receive the intervention, although the difference was not significant.…”

Section: Discussionmentioning

confidence: 99%

Effect of cyclosporin A intervention on the immunological mechanisms of coronary heart disease and restenosis

Wang

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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The present study aimed to investigate the effect of cyclosporin A (CSA) intervention on the immunological mechanisms underlying coronary heart disease (CHD) and restenosis (RS) in rabbits. A total of 48 rabbits were randomly divided into normal control (N), N + CSA, CHD model, CHD + CSA, RS model and RS + CSA groups. Rabbits in the respective groups received different treatments prior to sacrifice at the end of week 12. Iliac arteries were harvested from the rabbits for morphological analysis and to determine the mRNA and protein expression levels of cluster of differentiation (CD) 40/CD40 ligand (CD40L), CD134/CD134 ligand (CD134L) and inflammatory factors, including matrix metalloproteinase (MMP)-1, MMP-9, vascular cell adhesion protein (VCAM)-1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, by reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. As compared with the N group, the mRNA expression levels of MMP-9, VCAM-1 and TNF-α were significantly increased in the CHD and RS groups (P<0.05), but were significantly decreased in the groups with CSA intervention, as compared with those without CSA intervention (P<0.05). Conversely, there were no significant differences in the expression levels of MMP-1 and IL-6 among the six groups, although a decreasing trend of IL-6 expression was observed following intervention with CSA. Furthermore, there were significant differences in the mRNA and protein expression levels of CD40/CD40L and CD134/CD134L among the N, CHD and RS groups (P<0.05), and between the groups with and without CSA intervention. The present study demonstrated that CSA intervention exerted beneficial effects on CHD and RS, and further studies are required to investigate the mechanisms underlying the effects of CSA on CHD.

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Inflammatory cytokine profiles during Cyclosporin treatment for immunoglobulin-resistant Kawasaki disease

Cited by 37 publications

References 18 publications

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

Targeting Extracellular Cyclophilins Ameliorates Disease Progression in Experimental Biliary Atresia

Effect of cyclosporin A intervention on the immunological mechanisms of coronary heart disease and restenosis

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