OBJECTIVETo study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL).

METHODSA total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC).

RESULTSThe serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05).

CONCLUSIONSIL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

Acute Disease ; Atrial Natriuretic Factor ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Cholesterol ; blood ; Coronary Artery Disease ; blood ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Interleukin-1beta ; blood ; Interleukins ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Procalcitonin ; blood ; Protein Precursors ; blood ; Triglycerides ; blood

PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively analyzed 10-year data for patients with IVIG-resistant KD who were administered MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum body temperatures decreased significantly within 24 h of therapy. The patients' C-reactive protein levels were significantly lower 1 week after administering the first dose of MTX than those before treatment. No adverse effect for MTX was observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid defervescence, improvement of clinical symptoms, and normalization of acute-phase reactants in all patients. Thus, MTX could be a candidate treatment for IVIG-resistant KD.
C-Reactive Protein/analysis ; Child ; Child, Preschool ; Coronary Vessels/pathology ; Demography ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; Male ; Methotrexate/administration & dosage ; Methotrexate/therapeutic use ; Mucocutaneous Lymph Node Syndrome/blood ; Mucocutaneous Lymph Node Syndrome/drug therapy ; Retrospective Studies ; Steroids/therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the clinical efficacy of glucocorticoid combined with ulinastatin in the treatment of Kawasaki disease (KD) in children.

METHODSA total of 104 children who were admitted and diagnosed with typical KD between January 2011 and December 2013 were assigned to ulinastatin group (methylprednisolone+ulinastatin; n=46) and intravenous immunoglobulin (IVIG) group (n=58) according to the severity of KD and the willingness of their parents. Observations for the two groups were performed to compare the changes in coronary artery diameter before and at 1 week, 3 months, and 6 months after treatment, fever clearance time, retreatment condition, changes in white blood cells (WBC), platelets (PLT), hemoglobin (HB), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) at 1 week and 3 weeks after treatment, and total in-hospital cost.

RESYLTSThere was no significant difference in the coronary artery diameter between the two groups before or at 1 week, 3 months or 6 months after treatment (P>0.05). All the patients (100%) in the ulinastatin group vs 83% in the IVIG group had a normal body temperature after 48 hours of treatment (P<0.01). Two patients (4%) in the ulinastatin group and 10 patients (17%) in the IVIG group received retreatment. Significant differences were observed in ESR, WBC, and HB between them (P<0.01). The total in-hospital cost in the ulinastatin group was significantly lower than that in the IVIG group (P<0.01).

CONCLUSIONSFor children with KD, methylprednisolone combined with ulinastatin does not increase the risk of coronary artery aneurysm, decreases in-hospital costs, is superior in controlling laboratory markers and shortening the duration of fever during the acute phase compared with the IVIG therapy.

Blood Sedimentation ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Coronary Vessels ; pathology ; Drug Therapy, Combination ; Female ; Glucocorticoids ; administration & dosage ; Glycoproteins ; administration & dosage ; Health Care Costs ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; drug therapy ; pathology

OBJECTIVETo explore the correlation of heart rate variability (HRV) indices with cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in children with Kawasaki disease (KD) and their prognostic value.

METHODSA total of 130 children with KD were assigned into coronary artery lesion (CAL) group (n=47) and non-coronary artery lesion (NCAL) group (n=83). Meanwhile, 110 healthy children and 29 children in the recovery stage of non-cardiovascular diseases were selected as control and non-KD groups, respectively. Patients in the four groups received 24-hour HRV monitoring. Levels of serum cTnI and NT-proBNP were measured in the KD and the non-KD group.

RESULTSCompared with the controls of the same sex and age, the KD patients had significantly reduced standard deviation of all normal sinus RR intervals (SDNN), mean of SDNN (SDNN index), percentage of successive normal sinus RR intervals>50 ms (pNN50), very low frequency (VLF), low frequency (LF), and high frequency (HF) but a significantly increased LF/HF ratio (P<0.05). The HRV indices including SDNN, standard deviation of all mean 5-minute RR intervals (SDANN), SDNN index, root mean squared successive difference, pNN50, VLF, LF, and HF in the CAL group all significantly decreased compared with those in the control and non-KD groups, while the LF/HF ratio was higher in the CAL group than in the control group (P<0.05). The serum levels of cTnI and NT-proBNP in the CAL and NCAL groups were significantly higher than those in the non-KD group (P<0.05). In children with KD, serum cTnI level was negatively correlated with SDNN and HF but positively correlated with the LF/HF ratio (P<0.05); serum NT-proBNP level was negatively correlated with SDNN, SDANN, and HF (P<0.05).

CONCLUSIONSHRV indices have certain clinical significance in assessing CAL of children with KD.

Child ; Child, Preschool ; Coronary Vessels ; pathology ; Female ; Heart Rate ; physiology ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; physiopathology ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Troponin I ; blood

OBJECTIVETo detect plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) and analyze the relationship between NT-proBNP and other bio-markers in order to evaluate if NT-proBNP could be as a useful diagnostic marker to predict the risk of coronary arterial lesions in acute KD.

METHODTotally 106 patients with KD were recruited from January 2012 to April 2014 at Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology,64 were boys and 42 were girls, their age ranged from 2 months to 8 years and 4 months. Of the 106 cases, 48 had typical KD(TKD) and 58 incomplete KD(IKD). They were divided into two groups according to echocardiography results: coronary arterial lesions (KD-CAL, n = 33) and non coronary arterial lesions (KD-nCAL, n = 73). Forty children whose age and gender matched with respiratory tract infection were selected as control group, 22 were boys and 18 were girls, age range from 7 months to 7 years and 11 months. Plasma NT-proBNP levels were measured by using the enzyme-linked fluorescence analysis (ELFA) at the day of admission, meanwhile blood routine tests, liver function tests, determination of C-reactive protein (CEP), erythrocyte sedimentation rate (ESR), electrolytes were performed in these patients. Pearson's correlation analysis was used to evaluate the association. The ROC curve analysis was done to identify the threshold of coronary 'arterial lesions.

RESULTThe levels of NT-proBNP were (1 037 271) ng/L in TKD group and (1,325 ± 264) ng/L in IKD group. The levels of NT-proBNP in control group was (125 ± 22) ng/L. Both the levels of NT-proBNP in TKD and IKD group were significantly higher than that of control group (t = 3.360, 3.590; P < 0.05). The level of NT-proBNP in KD-CAL group was (2,775 ± 842) ng/L and that of KD-nCAL group was (830 ± 145) ng/L, NT-proBNP levels of KD-nCAL group was significantly higher than that of control group (t = 3.660, P = 0.007) ; moreover the level of NT-proBNP of KD-CAL group was also significantly higher than that of KD-nCAL group ( t = 3.860, P = 0.005). The levels of total white blood cell count, neutrophil percentage, platelet count, CRP and ESR of KD-CAL group were significantly higher than those of the control group, however there was no significant difference between KD-CAL group and KD-nCAL group. The levels of albumin and Na of KD-nCAL group were significantly lower than those of the control group. Plasma NT-proBNP level in KD group was positively correlated with white blood cell count, neutrophil percentage, and CRP (r = 0.239, P = 0.025; r = 0.359, P = 0.001; r = 0.474, P = 0.001), there was a negative correlation between albumin and Na (r = -0.303, P = 0.015; r = -0.338, P = 0.002). When the level of NT-proBNP was higher than 950 ng/L, the sensitivity for diagnosis of coronary arterial lesions in the KD was 88.1% and the specificity was 89.0%.

CONCLUSIONThe plasma NT-proBNP can be used as a useful parameter in early diagnosis of KD. Plasma NT-proBNP could be used to predict the risk of coronary arterial lesions in KD.

Biomarkers ; Blood Sedimentation ; C-Reactive Protein ; Case-Control Studies ; Child ; Child, Preschool ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Predictive Value of Tests ; ROC Curve ; Sensitivity and Specificity

OBJECTIVETo investigate the role of endogenous vascular elastase (EVE) in coronary artery between reconstruction among pediatric patients with Kawasaki disease (KD).

METHODSSixty children who were diagnosed with KD between January 2012 and April 2013 were selected as the case group, and peripheral venous blood samples were collected on days 0-11 (pathological stage I) and days 12-25 (pathological stage II) after the onset of disease; another 60 children without KD who visited the hospital due to acute fever during the same period were selected as the control group, and fasting peripheral venous blood samples were collected in the acute stage of fever. For both groups, serum levels of EVE and interleukin-6 (IL-6) and plasma vascular endothelial growth factor (VEGF) level were measured by enzyme-linked immunosorbent assay. For the case group, ultrasonic cardiography was used to detect coronary artery lesions (CALs) at the first, second and fourth weekends. The correlations of EVE level with IL-6 and VEGF levels were evaluated by Pearson correlation analysis.

RESULTSSerum levels of EVE and IL-6 in the case group in pathological stages I and II were significantly higher than in the control group (P<0.05), but plasma VEGF levels in stages I and II were significantly lower than in the control group (P<0.05); in the case group, EVE and IL-6 levels were significantly higher in stage II than in stage I (P<0.05). In pathological stage II, KD patients with CALs had significantly higher serum levels of EVE and IL-6 but significantly lower plasma VEGF levels compared with those without CALs (P<0.05); KD patients with coronary artery aneurysms (CAAs) had significantly higher serum levels of EVE and IL-6 but significantly lower plasma VEGF level compared with those without CAAs (P<0.05 for all). EVE level was positively correlated with IL-6 level (r=0.915, P<0.05), yet negatively correlated with VEGF level (r=-0.769, P<0.05).

CONCLUSIONSEVE may participate in coronary artery reconstruction in children with KD. To interfere EVE activity may reduce and prevent CALs.

Child ; Child, Preschool ; Coronary Artery Disease ; blood ; surgery ; Coronary Vessels ; surgery ; Female ; Humans ; Infant ; Interleukin-6 ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; pathology ; surgery ; Pancreatic Elastase ; blood ; physiology ; Reconstructive Surgical Procedures ; Vascular Endothelial Growth Factor A ; blood

Body fat is an important source of adipokine, which is associated with energy balance and inflammatory and immune responses. However, the role of adipokines in coronary artery complications in Kawasaki disease (KD) has not yet been fully explained. We investigated whether serum adipokine level can be a useful marker for patients with KD who are at higher risk of developing coronary artery lesion (CAL). We measured adipokine levels and other inflammatory parameters in 40 patients with KD, 32 febrile controls, and 15 afebrile controls. Interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and other laboratory parameters were also measured before and after intravenous immunoglobulin therapy, and in the convalescent phase. At admission, the serum resistin levels in KD children were significantly higher than those in controls (177.56 ng/mL in KD children, 76.48 ng/mL in febrile controls, and 17.95 ng/mL in afebrile controls). In patients with KD, resistin levels were significantly associated with decreased hemoglobin levels (P=0.049) and increased IL-6 levels (P=0.014). The serum IL-6 levels were significantly higher and body mass index was significantly lower in the group of KD with CALs than those without CALs (228.26 ng/mL vs. 39.18 ng/mL and 15.09 vs. 16.60, respectively). In conclusion, resistin is significantly elevated in KD patients, although it has no prognostic value of predicting coronary artery lesion in the acute stage.
Biological Markers/*blood ; Child ; Child, Preschool ; Coronary Vessels/pathology ; Echocardiography ; Female ; Hemoglobins/analysis ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Inflammation/blood/immunology ; Interleukin-6/*blood ; Male ; Mucocutaneous Lymph Node Syndrome/*blood/pathology ; Resistin/*blood ; Tumor Necrosis Factor-alpha/*blood

OBJECTIVETo investigate the expression of myeloid-related protein complex (MRP-8/14) in children with acute Kawasaki Disease (KD).

METHODSA total of 41 children with acute KD and 40 age- and sex-matched control children with upper respiratory tract infection were recruited. Serum levels of MRP-8/MRP-14 complex were measured by ELISA, messenger ribonucleic acid (mRNA) abundance of MRP-8 and MRP-14 in circulating granulocytes and monocytes was determined by RT-PCR, and the number of circulating endothelial cells was determined by flow cytometry.

RESULTSWhen the analysis was stratified according to the presence or absence of coronary artery ectasia in the KD patient group, serum levels of MRP-8/MRP-14 complex, MRP-8 and MRP-14 mRNA abundance in granulocytes, and the number of circulating endothelial cells were all significantly higher in KD patients with coronary artery ectasia than in KD patients without coronary artery ectasia (P<0.05). Serum levels of MRP-8/MRP-14 complex were positively correlated with the number of endothelial cells in the circulation (r=0.69, P<0.05).

CONCLUSIONSSerum levels of MRP-8/MRP-14 complex are elevated in a positive association with the number of circulating endothelial cells in KD children with coronary artery ectasia, suggesting a causative role in the development of coronary artery lesions.

Acute Disease ; Calgranulin A ; blood ; genetics ; physiology ; Calgranulin B ; blood ; genetics ; physiology ; Child, Preschool ; Coronary Artery Disease ; etiology ; Endothelial Cells ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; pathology ; RNA, Messenger ; analysis

OBJECTIVENumber and function of endothelial progenitor cell (EPC) and coronary artery lesion in Kawasaki disease (KD) model were evaluated to investigate therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF).

METHODC57BL/6 mice were injected with L. casei cell wall extract (LCWE); 48 mice were divided into 3 groups randomly: KD model group; G-CSF treated model group and control group, 16 in each. G-CSF was subcutaneously injected from day 5 to day 9 after injection of LCWE. Coronary artery lesion, number of circulating EPC and the function of bone marrow EPC were evaluated.

RESULTIn model group, inflammatory infiltration was found around coronary artery at 14 days. The number of circulating EPC was significantly decreased in model group (0.017% ± 0.008%) compared to control (0.028% ± 0.007%) (t = 2.037, P < 0.05). Disruption of elastin was consistently observed at 56 days. Stimulated by G-CSF, inflammatory infiltration was found around the coronary artery at day 14, while the number of circulating EPC (0.042% ± 0.015%) was increased significantly compared to models (t = 4.629, P < 0.05). At the day 56, the number of circulating EPC was decreased slightly (0.029% ± 0.012%), but still higher than the model group (t = 2.789, P < 0.05), and have no significant difference compared to controls (P > 0.05). Furthermore, there was no elastin disruption in the G-CSF group. In model group, bone marrow EPC's proliferation ability of absorbance (A value) was 0.38 ± 0.09 in thiazolyl blue assay, less than controls (0.61 ± 0.14, P < 0.01). Adhesion and migration function were down-regulated compared to controls [(3.1 ± 0.6) cells/HPF and (3.3 ± 0.6) cells/HPF vs. (6.4 ± 1.2) cells/HPF and (6.2 ± 0.5) cells/HPF, both P < 0.01]. In the G-CSF treated group, proliferation ability (A 0.58 ± 0.10), adhesion [(6.17 ± 1.13) cells/HPF], migration [(6.29 ± 0.42) cells/HPF] function were increased significantly compared to the model group (P < 0.01).

CONCLUSIONG-CSF can up-regulate EPC number and function to prevent coronary artery lesion in mice model of KD.

Animals ; Coronary Vessels ; drug effects ; pathology ; Disease Models, Animal ; Endothelial Cells ; cytology ; drug effects ; Flow Cytometry ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Mucocutaneous Lymph Node Syndrome ; blood ; drug therapy ; pathology ; Random Allocation ; Stem Cells ; cytology ; drug effects ; Up-Regulation

OBJECTIVETo study the roles of platelet (PLT) and its regulating factors, megakaryocyte, thrombopoietin (TPO) and transforming growth factor beta1 (TGF-beta1), in immune vasculitis in young rabbits.

METHODSAn experimental model of Kawasaki disease (KD) of weanling rabbits was reproduced by bovine serum. PLT count, total number and differentiating count of megakaryocyte, and serum TPO and TGF-beta1 levels were measured 0, 4, 8, 12, 16, 20, 24 and 28 days after KD induction. Pathological analysis of coronary artery, liver, spleen, kidney and brain was performed 17 and 28 days after KD induction.

RESULTSIn the KD group, PLT count, the total number of megakaryocyte, and the middle board megakaryocyte percentage increased 12, 16, 20, 24 and 28 days; serum TPO level increased 8, 12, 16, 20, 24 and 28 days; serum TGF-beta1 level increased 16, 20, 24 and 28 days after KD induction compared with those in the normal control group (p<0.05). The pathological examinations of coronary artery, liver, spleen, kidney and brain showed severe inflammatory injuries of tiny arteries and small/medium-sized arteries 17 and 28 days after KD induction, respectively in the KD group. The aortas were showed as mild inflammatory injuries.

CONCLUSIONSPLT, megakaryocyte, TPO and TGF-beta1 participate in the pathogenesis of KD, and they may play an important role in the injuries of immune vasculitis. This suggests that they may serve as markers for the assessment of severity in KD.

Animals ; Blood Platelets ; physiology ; Disease Models, Animal ; Humans ; Megakaryocytes ; physiology ; Mucocutaneous Lymph Node Syndrome ; etiology ; Rabbits ; Thrombopoietin ; physiology ; Transforming Growth Factor beta1 ; physiology ; Vasculitis ; etiology ; immunology ; pathology