Our previous study suggested that IVIG, the therapeutic agent of choice in acute KD, may prevent aneurysm formation through its ability to reduce TNF-α production and, thus, inhibit MMP-9 production indirectly. However, IVIG has no direct effect on MMP-9 production mediated by TNF-α[37]. Thus, the ability of atorvastatin

to mitigate MMP-9 production both indirectly through inhibition of TNF-α production and directly via inhibition of TNF-α-mediated ERK phosphorylation in SMC is very noteworthy and has important clinical implications. Our earlier studies in the animal model of KD revealed that whereas T cell proliferation and TNF-α production in the periphery occurred early following LCWE stimulation, TNF-α and MMP-9 production at the coronary arteries

were detected days later, corresponding to the late stage of the acute or subacute phase of Palbociclib ic50 KD in children indicating ongoing inflammation leading to elastin breakdown and end-organ damage [21,22]. Our results demonstrate a modulatory effect of atorvastatin at early (e.g. T cell activation and/or TNF-α production) as well as later (e.g. TNF-α-mediated MMP-9 production by SMC) events during disease progression, thus pointing to a potential therapeutic role of this agent even after immunological activation has taken place. This is relevant clinically, as systemic inflammation is well under way at diagnosis of KD, and atorvastatin, with its ability to interfere with both early and late pathogenic events, may be of added therapeutic value. There remain many factors to consider prior to clinical use of statin therapy in children with KD, especially in Selleck Etoposide the acute phase. The potential benefits of statin therapy during the acute inflammation of KD include its role in reducing both the cellular proliferative response

Doxacurium chloride and production of proinflammatory soluble mediators. Additionally, statin treatment can inhibit elastin degradation and matrix breakdown via down-regulation of MMP-9 production. Potential contraindications include hepatic toxicity evidenced by raised liver-derived enzymes. Liver dysfunction evidenced by elevation of transaminases is already common during acute KD, and in fact is one of the supportive laboratory criteria to help identify children with incomplete KD [1]. Additionally, limited toxicity data are available on statin use in young children, and young children comprise the at-risk population for KD. In children and adolescents with familial hypercholesterolaemia who are more than 8 years old, current evidence suggests that statin treatment is well tolerated without significant adverse concerns [38–41]; however, no data are available for those less than 5 years old, corresponding to the majority of children with KD. Before statin treatment can be initiated in very young children, additional pharmacokinetic and toxicity data are needed.