We evaluated the inflammatory indices according to the fever duration in children with Kawasaki disease (KD), and determined duration when the inflammatory processes in KD reach their peak. Children with KD (n=152) were classified into 7 groups according to fever duration: at the third day or earlier (n=20), fourth (n=33), fifth (n=46), sixth (n=15), seventh (n=15), eighth (n=9), and at the ninth day or later after fever onset (n= 14). The levels of various laboratory indices were determined 3 times: before, 24 hr and 7 days after intravenous immunoglobulin administration (2 g/kg). WBC and neutrophil counts, and C-reactive protein level were the highest at the sixth day. Levels of hemoglobin, albumin, and high density lipoprotein cholestrol were the lowest at the sixth day. Although these indices were not significant statistically between groups, the indices showed either bell-shaped or U-shaped distribution of which peak or trench were at the sixth day. These findiugs showed that the inflammatory processes in KD reach peak on the sixth day of fever onset. This finding is important because a higher single-dose intravenous immunoglobulin treatment before the peak day may help reduce the coronary artery lesions in KD.
Child, Preschool ; Coronary Vessels/pathology ; Female ; *Fever/blood ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; *Inflammation/blood/immunology ; Male ; *Mucocutaneous Lymph Node Syndrome/blood/immunology/pathology/therapy ; Time Factors

OBJECTIVEKawasaki disease (KD) is a febrile illness of childhood. The etiology of KD remains unknown. Multiple theories exist, including an infectious etiology and an immunological abnormality. Cardiac involvement ranges from myocarditis and pericarditis in the acute stage to the development of coronary artery aneurysms later in the course. The present study aimed to explore the effect of monocyte chemotactic protein-1 (MCP-1) in Kawasaki disease and its relationship with damage to the coronary arteries during the development of KD.

METHODSPlasma MCP-1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and MCP-1 mRNA expression in peripheral blood mononuclear cells (PBMC) was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in comparison of three groups: 56 patients with KD, 60 age-matched patients with non-infectious diseases, and 66 age-matched febrile patients with various diseases.

RESULTSPlasma MCP-1 concentration and MCP-1 mRNA expression in PBMC of patients with active KD [(409.55 +/- 97.42) pg/ml] and (1.97 +/- 0.77) were higher than those of control group. Plasma MCP-1 levels and MCP-1 mRNA expression of inactive KD group [(301.64 +/- 71.55) pg/ml] and (1.31 +/- 0.39) were significantly higher than those of non-infectious diseases patients. There was a marked increase in patients with inactive KD than those of non-infective patients, but there were no significant differences between inactive KD and febrile patients. Plasma MCP-1 levels and MCP-1 mRNA expression were markedly increased in KD patients with coronary artery lesions than those in patients without coronary artery lesions.

CONCLUSIONPlasma MCP-1 concentration and MCP-1 mRNA expression in PBMC were significantly increased in patients with KD, and they were higher in KD with coronary artery lesions. It indicates that MCP-1 may be a useful parameter for monitoring disease activity in patients with KD.

Chemokine CCL2 ; blood ; genetics ; metabolism ; Child ; Child, Preschool ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Leukocytes, Mononuclear ; metabolism ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; genetics ; pathology ; RNA, Messenger ; genetics

This study was designed to evaluate the therapeutic effect between single(A group) and five-day(B group) administration of IV gammaglobulin in the patients with Kawasaki disease from June 1987 to September 1993, who were admitted to the Department of Pediatrcs, Hanyang University College of Medicine. The clinical and echocardiographic results were as follows. 1) Of 90 cases, 40 cases belong to A group, and 50 cases to B group. The ratio of male to female was 2.60 : 1, and 85% of A group and 76% of B group was under the age of 3 years. 2) In 90% of A group and 88% of B group, peak level of platelet count was above 400,000.mm3, and as a whole peak level of platelet in 88.9% above 400,000/mm3. 3) Complications in S group were hepatitis(22.5%), coronary arterial involvement(12.5%), and gall bladder hydrops(7.5%), and in B group hepatitis(26%), gall bladder hydrops(18%), coronary arterial involvement(12%), pericardial effusion(4%), and meningitis(2%). 4) All 5 cases with mild coronary arterial dilatation in a group had improved in follow up echocardiography after 6 months. And in B group, 5 of 6 cases with coronary arterial involvement had improved, but coronary pathology in one case with large coronary aneurysm sustained after 2 years. In conclusion, we could not find the significant difference in reduction of the duration of illness or the coronary arterial disease between two groups, but we recommend single intravenous infusion of gammaglobulin as soon as possible to prevent severe coronary arterial disease.
Blood Platelets ; Coronary Aneurysm ; Dilatation ; Echocardiography ; Female ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Male ; Mucocutaneous Lymph Node Syndrome* ; Pathology ; Platelet Count ; Urinary Bladder

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

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

OBJECTIVEKawasaki disease (KD) complicated with coronary artery lesion (CAL) seriously threatens survival quality and life of patients, suggesting that it is very important to early predict the risk of CAL and to early diagnose the disease. Nevertheless, up to now there has been no specific clinical biochemical marker for it because of the poor understanding of the pathological process of KD with CAL. Matrix metalloproteinases (MMPs) and their specific tissue inhibitor of metalloproteinases (TIMPs) play an important role in arterial wall extracellular matrix breakdown and remodeling and are involved in CAL in other diseases. In the present study the practical value of serum MMP-9 and TIMP-1 levels in the prediction and early diagnosis of CAL in KD patients was investigated.

METHODSAll subjects were from Chinese population. Serum levels of MMP-9 and TIMP-1 were measured by rapid one-step sandwich enzyme immunoassay in 59 KD patients including 15 with CAL and 44 without CAL by 2 D-echocardiography and coronary angiography, and 20 normal healthy children as controls. Blood samples of patients were obtained before and after intravenous immunoglobulin (IVIG) treatment in acute stage, subacute stage and convalescent stage as well. Serum MMP-9 and TIMP-1 levels and the ratio of MMP-9/TIMP-1 were compared by statistical method in KD patients and controls, as well as in KD with CAL and without CAL.

RESULTSIn acute stage serum MMP-9 and TIMP-1 levels and the ratio of MMP-9/TIMP-1 were higher (P < 0.01) in patients with KD than those in healthy children. After IVIG treatment in KD patients serum MMP-9 level and the ratio of MMP-9/TIMP-1 decreased (P < 0.01). Before IVIG treatment serum MMP-9 level and the ratio of MMP-9/TIMP-1 were higher (P < 0.01) in patients with CAL than those in patients without CAL, and in acute stage after IVIG treatment serum MMP-9 level of KD patients with CAL was still higher than that of KD patients without CAL.

CONCLUSIONIn acute stage of KD serum MMP-9 level and the ratio of MMP-9/TIMP-1 were higher in patients with CAL than those in patients without CAL, suggesting that during acute phase of KD the great increase in serum MMP-9 and the imbalance of the MMP-9/TIMP-1 ratio might be high risk factors of KD coronary artery lesion. Therefore, the measurement of serum MMP-9 and TIMP-1 might be of important clinical value in the prediction and the early diagnosis of KD with coronary artery lesion.

Biomarkers ; blood ; Case-Control Studies ; Child ; Child, Preschool ; Coronary Artery Disease ; blood ; complications ; diagnosis ; pathology ; Female ; Humans ; Infant ; Male ; Matrix Metalloproteinase 9 ; blood ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Tissue Inhibitor of Metalloproteinase-1 ; 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

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 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

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