Interleukin-18 and coronary artery lesions in patients with Kawasaki disease.

BACKGROUND: Interleukin-18 (IL-18) plays an important role in mediating cytokine cascade leading to coronary artery lesions (CALs) in Kawasaki disease (KD). However, our research suggested that the literature regarding IL-18 and KD is limited. Consequently, this study aimed to evaluate the correlation between IL-18 and CALs in patients with KD. METHODS: In this prospective study of 14 children with KD (seven without and seven with CALs in the acute phase), we obtained patient measurements of a series of serum IL-18 levels in the acute, subacute, and convalescent phases. Serum IL-18 levels were measured with a Bio-Plex cytokine assay. Control samples were obtained from 18 febrile children with viral infection. RESULTS: Compared with febrile controls, patients with acute-stage CALs [postintravenous immunoglobulin (post-IVIG) period] had a significantly higher IL-18 level (88.4 ± 20.7 vs 56.0 ± 35.0 pg/mL, p = 0.006). However, those without acute-stage CALs (post-IVIG period) lacked similarly elevated IL-18 level readings (62.0 ± 40.6 vs 56.0 ± 35.0 pg/mL, p = 0.762). The IL-18 level of patients with acute-stage CALs did not decrease significantly until the convalescent phase (97.4 ± 55.8 vs 38.7 ± 22.6 pg/mL, p = 0.018), but for those without CALs, it decreased significantly in the subacute phase (60.2 ± 37.4 vs 23.6 ± 13.8 pg/mL, p = 0.018). In the subacute stage, there was a significant difference of IL-18 level between patients with and without acute-stage CALs (p = 0.048). CONCLUSION: Our data show that IL-18 levels were elevated in the acute phase of KD and might be related to the formation of CALs.

Clinical relevance of the risk factors for coronary artery lesions in Kawasaki disease.

We aimed to investigate which factors are associated with coronary artery lesions (CALs) during the acute and chronic stages in Taiwanese children with Kawasaki disease (KD). A total of 216 children with KD were enrolled. Clinical and laboratory data were obtained for each child within 7 days of illness. The patients were classified into KD children without acute CALs (n=135) and those with acute CALs (n=81) according to echocardiography data at Week 2 after treatment. Then, KD children with acute CALs were further divided into those without chronic CALs (n=55) and with chronic CALs (n=26) according to annual echocardiography data. During acute stage of KD, neutrophil count (<54%) [odds ratio (OR)=0.44, p=0.041]; second dose of intravenous immunoglobulin (IVIG) treatment (OR=5.01, p=0.009); and platelet count (≤400,000) (OR=0.42, p=0.006) were correlated with the risk of acute CALs. During chronic stage of KD, age (12-60 months) (OR=0.25, p=0.042); first dose of IVIG treatment (OR=0.12, p=0.005); and band count (≥3%) (OR=3.51, p=0.032) were correlated with the risk of chronic CALs. Our results suggest that the effects of neutrophil count, doses of IVIG treatment, and platelet count on CALs in acute KD are important. Age, doses of IVIG treatment, and band count are related to the persistence of CALs in chronic stage of KD.

Recent advances in the treatment of Kawasaki disease.

Kawasaki disease (KD) is acute systemic vasculitis that occurs mainly in infants and children under 5 years of age. The etiology of KD remains unknown. KD is liable to be complicated by coronary artery lesions (CALs), which develop in approximately 15-25% of untreated KD children and in approximately 5% of KD children after intravenous immunoglobulin (IVIG) therapy. A single high dose of IVIG (2 g/kg) is the gold standard therapy in the acute stage of KD. However, approximately 8--38% of children are unresponsive to initial IVIG treatment and at increased risk for CAL development. Anti-inflammatory high doses of aspirin are recommended in conjunction with IVIG, but our study demonstrated that there is no evidence of efficacy in preventing CAL development. The usefulness of steroids in initial therapy for KD or treatment of IVIG-resistant patients is not well established. Other immunosuppressive therapies, including infliximab, have been used in the treatment of refractory KD, but merit additional investigation. Subclinical atherosclerosis may develop early in KD patients, which makes early initiation of therapy to improve chronic inflammation an important issue. Future multicenter studies may help to define the optimal management of KD patients.

Cytokine genetic polymorphisms and susceptibility to Kawasaki disease in Taiwanese children.

BACKGROUND: The relationship between cytokine gene polymorphisms and susceptibility to Kawasaki diseases (KD) is still controversial, so the aim of the present study was to investigate the association of 14 various polymorphisms of 9 cytokine genes (interleukin (IL)-1A, IL-1B, IL-1RN, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-A and transforming growth factor-B) with KD risk. METHODS AND RESULTS: A total of 211 KD children and 221 adult controls were recruited. All controls were frequency matched to KD patients on sex and ethnicity. PCR and TaqMan assays were used for genotyping. There were no significant differences between KD children and adult controls in the genotype or allelic type frequencies of the 14 polymorphisms. No significant associations were found between haplotypes, constructed by IL-1B, IL-4, IL-8, and IL-10 cytokine genes, and risk of KD. Additionally, a linear trend was observed when these single nucleotide polymorphisms were combined, as evidenced by an increasing risk of KD as the number of at-risk genotypes increased (P(linear trend)=0.002). In the stratification analysis of age and sex, there was a linear trend of KD risk as the number of at-risk genotypes increased among those aged >12 months (P=0.014) or female (P=0.001), respectively. CONCLUSIONS: No associations between individual cytokine genetic polymorphisms and susceptibility of KD were observed, but a gene-dosage effect on the risk of KD was found, especially for older or female subjects.