ABSTRACT
BACKGROUND: Kawasaki disease (KD), a systemic vasculitis, is suspected to be related to abnormalities in innate immunity. Based on the important role of IL-1 signaling in innate immunity, we investigated the effects of an anti-IL-1ß antibody using a Candida albicans water-soluble fraction (CAWS)-induced mouse model of KD. METHODS: CAWS (0.5 mg/mouse) was injected intraperitoneally into 5-week-old DBA/2 mice on five consecutive days. An anti-Murine IL-1ß antibody (01BSUR) was administered at various doses (2.5, 5.0, and 10.0 mg/kg) and time points (2 days before, same day, and 2, 5, 7, and 14 days after CAWS administration). After 4 weeks, vasculitis in the aortic root was investigated histologically. Cytokines including IL-1ß, -6, -10, and TNF-α were also measured. RESULTS: Groups administered 01BSUR at all doses showed a significant reduction in the area of vasculitis. In addition, 01BSUR inhibited vasculitis until 7 days after CAWS administration. In the analysis of various time points, the level of IL-6 was lower in all groups compared to the CAWS only group, but the levels of IL-1ß, TNFα, and IL-10 were lower when 01BSUR was administered before CAWS. On the other hand, TNFα and IL-10 levels were restored when 01BSUR was administered after CAWS, suggesting that 01BSUR may have additional effects beyond blocking IL-1ß signaling. CONCLUSIONS: The anti-IL-1ß antibody significantly attenuated CAWS-induced vasculitis. The mechanism of inhibiting vasculitis is thought to include inhibition of the IL-1ß pathway and additional effects beyond blocking IL-1ß signaling.
Subject(s)
Antibodies/administration & dosage , Interleukin-1beta/immunology , Interleukin-1beta/metabolism , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/immunology , Animals , Antibodies/pharmacology , Aorta/pathology , Disease Models, Animal , Immunity, Innate , Interleukin-10/metabolism , Interleukin-6/metabolism , Male , Mice, Inbred DBA , Mucocutaneous Lymph Node Syndrome/pathology , Signal Transduction/drug effects , Signal Transduction/immunology , Time Factors , Tumor Necrosis Factor-alpha/metabolismABSTRACT
AIMS: We evaluated the systolic and diastolic functions of both ventricles from the early neonatal period to adolescence using color tissue Doppler imaging and 2-dimensional tissue tracking echocardiography. METHODS: We examined 100 healthy children (aged 1-5 days, n = 20; 1 month, n = 20; 1 year, n = 20; 6-7 years, n = 20; and 12-13 years, n = 20). Blood flow velocities in the mitral and tricuspid valves (E) were obtained with pulsed Doppler imaging, and longitudinal systolic (S') and early diastolic (E') peak velocities at the mid free wall segment of both ventricles were obtained with color tissue Doppler imaging. For longitudinal strain imaging, systolic peak values were obtained at the same position. In addition, peak systolic radial strain was obtained from a short-axis view of the left ventricle using the tissue tracking method. The E/E' ratio was calculated. RESULTS: Regarding systolic indices, S' increased during development and stabilized at 6 to 7 years, and longitudinal strain reached values of the 12- to 13-year-old group at 1 year of age in both ventricles. Like longitudinal strain, radial strain in the left ventricle reached values of the 12- to 13-year-old group at the age of 1 year. Similarly, the E/E' ratio was high at 1 month or younger and decreased by 1 year. CONCLUSIONS: Systolic and diastolic variables change markedly from birth to 1 year of age and show only small changes thereafter.
