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

Antibodies, Anticardiolipin ; blood ; Autoantibodies ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; immunology ; beta 2-Glycoprotein I ; immunology

OBJECTIVETo investigate the changes in the expression levels of peripheral blood T helper 9 (Th9) cells and cytokine interleukin-9 (IL-9) in children in the acute stage of Kawasaki disease (KD) and their clinical significance.

METHODSA total of 45 children in the acute stage of KD who were treated from April 2014 to July 2015 were enrolled, and the children were followed up in the recovery stage. Another 45 healthy children who underwent physical examination were enrolled as the control group. Flow cytometry was used to measure the percentage of peripheral blood Th9 cells, and ELISA was used to measure the serum level of IL-9.

RESULTSThe children in the acute stage of KD showed a significantly higher percentage of Th9 cells and a significantly higher serum level of IL-9 compared with those in the recovery stage and the control group (P<0.05). The percentage of Th9 cells and serum level of IL-9 showed no significant differences between the children in the recovery stage and those in the control group (P>0.05). In the acute stage, the percentage of Th9 cells was positively correlated with the levels of IL-9, C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), platelet count (PLT), and globulin (r=0.624, 0.324, 0.402, 0.382, 0.467, and 0.386 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.306, P<0.05). The serum level of IL-9 was positively correlated with the levels of CRP, PCT, ESR, PLT, and globulin (r=0.365, 0.456, 0.403, 0.423, and 0.453 respectively, all P<0.05), but negatively correlated with serum albumin (r=-0.343, P<0.05).

CONCLUSIONSThe children in the acute stage of KD show significant increases in the percentage of peripheral Th9 cells and serum cytokine IL-9 level, which return to normal in the recovery stage. In the acute stage of KD, the expression levels of Th9 and IL-9 are closely correlated with laboratory markers. The results suggest that Th9 cells and IL-9 play important roles in the pathogenesis and outcome of KD.

Acute Disease ; Blood Sedimentation ; C-Reactive Protein ; analysis ; Child, Preschool ; Female ; Humans ; Infant ; Interleukin-9 ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology

Serum IL-10 level in Kawasaki disease(KD) was tested. In the KD patients' sera during the acute phase, the levels of IL-10 were markedly elevated (122.0 +/- 39.1 pg/ml) compared to 3.7 +/- 1.7 pg/ml in the control subjects (p< 0.001). The serum IL-10 levels remained elevated in the subacute phase (16. 7 +/- 9.7 pg/ml, p< 0.001) and were restored to the normal levels(7.9 +/- 3.9 pg/ml) during the convalescent phase. In the patients with acute febrile disease, the serum IL-10 level increased significantly (34.4 +/- 14.1 pg/ml, p< 0.001) compared to that of the age-matched control subjects, but were not as high as in acute phase of KD(p< 0.005). This increase in serum IL-10 levels in KD may contribute to the up-regulation of humoral immunity and to the down-regulation of acute inflammation due to an increase in proinflammatory cytokines.
Child ; Child, Preschool ; Female ; Human ; Infant ; Interleukin-10/*blood ; Interleukin-12/blood ; Interleukin-4/blood ; Male ; Mucocutaneous Lymph Node Syndrome/blood/*immunology ; Support, Non-U.S. Gov't

OBJECTIVETo study the clinical significance of anti-endothelial cell antibodies (AECA) and anti-neutrophil cytoplasmic antibodies (ANCA) in Kawasaki disease (KD) and its complication of coronary arterial lesions (CAL).

METHODSForty-two children with KD, as well as 20 children with fever caused by respiratory infection (fever control group) and 15 children for selective operation (normal control group), were included in the study. Serum levels of AECA and ANCA were measured using enzyme-linked immunosorbent assay. Echocardiography was performed to evaluate CAL in KD patients.

RESULTSDuring the acute phase, the KD patients had significantly higher serum AECA and ANCA levels than the two control groups (P<0.01). The KD patients had reduced serum ANCA levels (P<0.01) in the remission phase, but they were still higher than those of the two control groups (P<0.05). Among KD patients, those with CAL had significantly higher ANCA levels than those without CAL (P<0.01) in the acute phase. There was a positive correlation between serum ANCA levels and the ratio of left coronary artery to aortic annular diameter in KD patients with CAL (r=0.88, P<0.01).

CONCLUSIONSAECA and ANCA may be involved in vasculitis and CAL among children with KD. Serum levels of AECA and ANCA may be used as indicators for the diagnosis of suspected KD cases in the acute phase. Elevated ANCA level has a certain predictive value for CAL.

Antibodies, Antineutrophil Cytoplasmic ; blood ; Autoantibodies ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; immunology ; Severity of Illness Index

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

OBJECTIVETo study the role of triggering receptor expressed on myeloid cells-1(TREM-1) in the pathogenesis of Kawasaki disease (KD).

METHODSBased on color Doppler examination results, 45 children with KD were classified into two groups: coronary artery lesions (CAL group) and no coronary artery lesions (NCAL group). Fifteen children with fever caused by respiratory infection (fever control group) and fifteen healthy children (normal control group) served as controls. Real-time fluorescence quantitative PCR was used to detect the expression of TREM-1 mRNA and DNAX-activating protein 12 (DAP12) mRNA in peripheral blood mononuclear cells (PBMC). ELISA was used to detect the expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), DAP12, monocyte chemoattractant protein-1(MCP-1), interleukin-8 (IL-8) proteins levels.

RESULTSThe mean serum protein concentrations of sTREM-1 and DAP12 and the expression levels of TREM-1 mRNA and DAP12 mRNA in PBMC in 45 children with KD (KD group) were significantly higher than in the two control groups (P<0.05). The levels of sTREM-1 protein and TREM-1 mRNA in the CAL subgroup were significantly higher than in the NCAL subgroup (P<0.05). The serum protein concentrations of MCP-1 and IL-8 in the KD group were significantly higher than in the two control groups (P<0.05). The MCP-1 protein level in the CAL subgroup was significantly higher than in the NCAL subgroup (P<0.05). In children with KD, there was a positive correlation between serum sTREM-1 and MCP-1 levels (r=0.523, P<0.05).

CONCLUSIONSTREM-1 activation may be involved in the development of KD.

Chemokine CCL2 ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interleukin-8 ; blood ; Male ; Membrane Glycoproteins ; blood ; genetics ; physiology ; Mucocutaneous Lymph Node Syndrome ; etiology ; immunology ; RNA, Messenger ; analysis ; Receptors, Immunologic ; blood ; genetics ; physiology ; Triggering Receptor Expressed on Myeloid Cells-1

We investigated whether the production and gene expression of Gro-alpha and RANTES in Kawasaki disease differ in measles. Forty-two samples from 14 patients in different clinical stages of Kawasaki disease, eight samples from 8 patients in the acute stage of measles and seven samples from 7 healthy children were collected. The present study was performed using ELISA and RT-PCR for the productions and gene expression of the chemokines. The production of Gro-alpha was markedly elevated during the acute stage of measles compared with Kawasaki disease. Moreover, the expression of Gro-alpha was increased in every case of measles, but not in Kawasaki disease. The production of RANTES was elevated in the acute stage of both diseases when compared to the healthy control. However, the plasma RANTES level did not change significantly according to the clinical stages of Kawasaki disease. A correlation between the production and gene expression of RANTES and Gro-alpha was not found in Kawasaki disease. These results suggest that Kawasaki disease differs from measles with regard to Gro-alpha production and expression, but not RANTES. Gro-alpha might play an important role in the acute stage of measles, however not in Kawasaki disease. Further studies are needed to clarify the efficacy of Gro-alpha as a marker in measles.
Biological Markers ; Chemokines/blood/*genetics ; Chemotactic Factors/blood/*genetics ; Child ; Child, Preschool ; Comparative Study ; Female ; Gene Expression/immunology ; Human ; Infant ; Intercellular Signaling Peptides and Proteins/blood/*genetics ; Leukocytes, Mononuclear/*physiology ; Male ; Measles/*immunology/physiopathology ; Mucocutaneous Lymph Node Syndrome/*immunology/physiopathology ; RANTES/blood/*genetics ; RNA, Messenger/analysis

Acute Disease ; Case-Control Studies ; Child ; Child, Preschool ; Female ; GATA3 Transcription Factor ; genetics ; Humans ; Infant ; Interferon-gamma ; genetics ; Interleukin-4 ; genetics ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; genetics ; immunology ; RNA, Messenger ; Reverse Transcriptase Polymerase Chain Reaction ; T-Box Domain Proteins ; genetics ; Th1 Cells ; immunology ; Th2 Cells ; immunology