Matrix Metalloproteinases, Tissue Inhibitors and Cytokines in Patients with Kawasaki Disease

Cho, Ae Ra; Hong, Young Mi

Abstract

PURPOSE
Kawasaki disease(KD) is a multisystemic inflammatory vasculitis of unknown etiology, but immunological abnormalities have been documented and implicated in the pathogenesis of KD. Matrix metalloproteinases(MMPs) have proteolytic activity against connective tissue proteins, and increased activity of MMPs and a quantitative imbalance between MMP and tissue inhibitor of MMP (TIMP) can result in several pathologic conditions. MMP and TIMP may also be involved in the formation of coronary arterial lesions in KD.
METHODS
Serum levels of MMP1, MMP2, MMP9, TIMP1, TIMP2, interleukin(IL)-6 and tumor necrosis factor(TNF)-alpha were measured in 27 KD patients(group I, 10 patients with normal coronary artery; group II, 17 patients with coronary arterial lesions) and 15 healthy children(group III). Blood samples from each study group were drawn before and after intravenous immunoglobulin(IVIG) therapy and in the convalescent stage.
RESULTS
The MMP9 levels and MMP9/TIMP2 ratios before and after IVIG therapy were significantly higher in group II. The MMP9 levels were significantly higher before IVIG therapy, and decreased through the convalescent stage. The IL-6 and TNF-alpha levels were also significantly higher in group II than in the other groups. The serum MMP9 levels showed significantly positive correlation with the circulating leukocyte counts and IL-6 levels.
CONCLUSION
The increased levels of MMP and the imbalance between MMP and TIMP increase the susceptibility to the coronary arterial lesions in KD. The cytokines including IL-6 and TNF-alpha are also important in the activation of MMP and formation of coronary arterial lesions in KD.