Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
Adolescent ; Biomarkers ; blood ; C-Reactive Protein ; Chronic Disease ; Cytokines ; Depressive Disorder, Major ; blood ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; blood ; complications ; Histamine ; blood ; Homocysteine ; blood ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin G ; blood ; immunology ; Inflammation Mediators ; blood ; Male ; Risk Factors ; S100 Calcium Binding Protein beta Subunit ; blood ; Young Adult

Gastric cancer (GC) is one of the most common tumor in the world, and remains a major public health problem and one of the leading causes of death. Recently many researches have demonstrated that systemic inflammatory response is associated with prognosis and response to therapy in gastric cancer, and the peripheral blood count test can partly reflect the systemic inflammatory response. Based on the peripheral blood count test, there are a lot of research regarding the relation between the platelet count (PLT), neutrophil, lymphocyte, white blood cell (WBC), neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio (PLR) with their prognostic role in gastric cancer. A high PLT and preoperative lymphocytopenia are both associated with increased lymph node metastasis, stage (III(+IIII(), serosal invasion (T3+T4) risk and poorer overall survival. Besides above, platelet monitoring following surgery can be applied to predict the recurrence for patients with GC that suffer preoperative high PLT but have restored PLT levels following resection. Moreover systemic inflammatory factors based on blood parameters, such as PLR, NLR and so on, have relation with the poor prognosis of patients with GC. Among them, high NLR is a negative predictor of prognosis in GC patients. However PLR remains inconsistent, while most researches demonstrated high PLR may be useful prognostic factor rather than independent prognostic factor. There are still some limitations which include various cut-off values, little of clinician attention, the uncertain mechanism, etc. Here we review the research progress in the prognostic role of the blood count test in gastric cancer.
Blood Cell Count ; methods ; statistics & numerical data ; Blood Platelets ; physiology ; Humans ; Inflammation ; blood ; diagnosis ; immunology ; Leukocyte Count ; statistics & numerical data ; Lymphatic Metastasis ; diagnosis ; immunology ; Lymphocyte Count ; statistics & numerical data ; Lymphopenia ; blood ; physiopathology ; Neoplasm Invasiveness ; immunology ; Neoplasm Recurrence, Local ; blood ; diagnosis ; Neoplasm Staging ; statistics & numerical data ; Neutrophils ; immunology ; Platelet Count ; statistics & numerical data ; Prognosis ; Stomach Neoplasms ; blood ; diagnosis ; immunology ; mortality ; Treatment Outcome

Objective To investigate the changes of regulatory T cells (Tregs) and whether Tregs can modulate the distribution of macrophage subtypes in visceral adipose tissue in the early stage of obesity.Methods After C57BL/6 mice obesity models were successfully established,metabolic parameters and numbers of Tregs and M1/M2 macrophage were measured at 4,10,and 20 weeks.The changes of metabolic parameters and adipose tissue inflammation in obesity mice after rapamycin intervention were evaluated. Results The early-stage obesity models were successfully established.Compared with normal diet mice,high fat diet mice had significantly higher epididymal adipose tissue mass and serum leptin levels(P<0.05).However,there was no statistical difference in blood glucose and insulin levels between these two groups(All P>0.05). Macrophages infiltration in adipose tissue in high fat diet mice gradually increased with time,coincident with decrease in Treg numbers. Increased numbers of Treg,improved metabolic parameters,and decreased ratio of M1/M2 can be seen after rapamycin intervention in mice.Conclusion The decrease of Tregs in the early stage of obesity may contribute to abnormal distribution of macrophage subtypes in visceral adipose.
Animals ; Blood Glucose ; Diet, High-Fat ; Inflammation ; Intra-Abdominal Fat ; cytology ; Leptin ; blood ; Macrophages ; cytology ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity ; immunology ; T-Lymphocytes, Regulatory ; cytology

OBJECTIVETo investigate the effect of continuous veno-venous hemofiltration (CVVH) on inflammatory mediators in children with severe hand, foot and mouth disease (HFMD), and to investigate its clinical efficacy.

METHODSA total of 36 children with stage IV HFMD were enrolled and randomly divided into conventional treatment group and CVVH group (n=18 each). The children in the CVVH group were given CVVH for 48 hours in addition to the conventional treatment. The levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and lactic acid in peripheral venous blood, heart rate, blood pressure, and left ventricular ejection fraction were measured before treatment and after 24 and 48 hours of treatment.

RESULTSAfter 24 hours of treatment, the conventional treatment group had a significantly reduced serum IL-2 level (P<0.01), and the CVVH treatment group had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.05). After 48 hours of treatment, both groups had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.01), and the CVVH group had significantly lower levels of these inflammatory factors than the conventional treatment group (P<0.01). After 48 hours of treatment, heart rate, systolic pressure, and blood lactic acid level were significantly reduced, and left ventricular ejection fraction was significantly increased in both groups, and the CVVH group had significantly greater changes in these indices except systolic pressure than the conventional treatment group (P<0.01).

CONCLUSIONSCVVH can effectively eliminate inflammatory factors, reduce heart rate and venous blood lactic acid, and improve heart function in children with severe HFMD.

Child, Preschool ; Cytokines ; blood ; Female ; Hand, Foot and Mouth Disease ; immunology ; physiopathology ; therapy ; Hemodynamics ; Hemofiltration ; Humans ; Infant ; Inflammation Mediators ; blood ; Male ; Ventricular Function, Left

OBJECTIVETo investigate the effects of prophylactic administration of all-trans retinoic acid (ATRA) in relieving inflammation in a rat model of collagen-induced arthritis (CIA).

METHODSFemale Wistar rats (6 to 8 weeks old) were randomly divided into normal control group, solvent control group, and prophylactic ATRA treatment (0.05, 0.5, and 5 mg/kg) groups. All the rats except for those in normal control group were subjected to subcutaneous injection of type II collagen and incomplete Freund adjuvant in the tails to induce CIA, followed by injection on the following day with saline, corn oil or different doses of ATRA 3 times a week. The arthritis index (AI) scores, histological scores, serum levels of TNF-α, IL-17A, and IL-10, and expressions of proteases related with cartilage damage were evaluated.

RESULTSOn the 15th day after the primary immunization, the AI scores increased significantly in all but the normal control groups; the scores increased progressively in all the 3 ATRA groups but remained lower than that in the solvent control group, which was stable over time. The rats in the 3 ATRA groups showed obvious pathologies in the knee and ankle joints, but the semi-quantitative scores of pathology damage showed no significance among them. Compared with those in solvent control group, the serum IL-17A and TNF-α levels decreased, serum IL-10 level increased, and the expressions of ADAMT-4 and MMP-3 proteins decreased significantly in the knees in the 3 ATRA groups.

CONCLUSIONATRA can reduce the production of TNF-α and IL-17A and increase the production of IL-10 to alleviate the inflammation in rats with CIA. ATRA may delay the progression of RA by correcting the imbalance of Th1/Th2 and Th17/Treg.

ADAMTS4 Protein ; metabolism ; Animals ; Arthritis, Experimental ; chemically induced ; drug therapy ; Collagen Type II ; Female ; Freund's Adjuvant ; Inflammation ; drug therapy ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Lipids ; Matrix Metalloproteinase 3 ; metabolism ; Rats ; Rats, Wistar ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology ; Tretinoin ; pharmacology ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the regulation of adipose-derived mesenchymal stem cells (ADSC) on helper T cells and regulatory T cells in allergic rhinitis(AR) mouse model and the underlying mechanisms.

METHODSUsing random number table, 60 Balb/c mice were divided into 6 groups (represented by: sensitized/challenged/treated ), they were the experimental group 1(OVA/OVA/high dose ADSC), the experimental group 2(OVA/OVA/low dose ADSC), the experimental group 3(OVA/OVA/PBS), the experimental group 4(OVA/OVA/0), the control group 1(PBS/PBS/0) and the control group 2(0/0/0). The mouse ADSC were isolated and cultured through conventional method, and AR mouse model was built with OVA and aluminum. The mice were injected with high (3×10(6)), low (1×10(6)) ADSC respectively labeled by CM-Dil for 3 consecutive days via tail-vein injection and sacrificed 48 hours later. Finally, levels of IL-4, IL-6, IL-10 and IFN -γ in serum were examined by ELISA; expressions of the four cytokines in spleen were examined by q RT-PCR; migration of ADSC to mouse model nasal mucosa were observed through fluorescence microscope; eosinophil infiltration were observed by the nasal HE staining.

RESULTSMouse ADSC was isolated, cultured and identified successfully. There was significant difference in symptom scores of AR models (compared with 0/0/0 group, P<0.01). The IL-4 and IL-6 levels of OVA/OVA/high ADSC group were significantly lower than OVA/OVA/0 group (group 1: (17.95±7.78), (27.51±5.93) pg/ml; group 4: (56.82±9.12), (70.03±7.22) pg/ml), the IFN-γ and IL-10 levels increased significantly (group 1: (367.74±13.79), (417.10±72.40) pg/ml; group 4: (199.46±11.25), (122.50±15.57) pg/ml) in serum. These differences were statistically significant(P<0.01). Compared with OVA/OVA/low ADSC group, the IL-4 and IL-6 levels decreased significantly (group 1: (17.95±7.78), (27.51±5.93) pg/ml; group 2: (41.57±12.27), (56.21±9.23)pg/ml) of OVA / OVA / high ADSC group, and the IFN-γ and IL-10 increased significantly (group 1: (367.74±13.79), (417.10±72.40)pg/ml; group 2: (281.77±30.41), (203.45±87.10) pg/ml). These differences were statistically significant(P<0.01). At the same time, the corresponding changes observed at the levels of the cytokines' mRNA. ADSC labeled by CM-Dil could migrate to the mouse nasal mucosa. OVA/OVA/high ADSC group showed the more red fluorescence than the OVA/OVA/low ADSC group. The eosinophils in nasal mucosa of the two groups reduced compared with the normal control.

CONCLUSIONADSC injected via tail-vein can migrate to nasal mucosa and play non-specific immune effects, that may to effect the releases of some cytokines then to regulate the Th1/Th2 imbalance and the function of Treg cell, finally that be dose-related in a certain extent.

Adipose Tissue ; cytology ; Animals ; Cytokines ; blood ; Disease Models, Animal ; Eosinophils ; immunology ; Inflammation ; Mesenchymal Stem Cell Transplantation ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; immunology ; Rhinitis, Allergic ; immunology ; therapy ; T-Lymphocytes, Helper-Inducer ; immunology ; T-Lymphocytes, Regulatory ; immunology

BACKGROUND/AIMS: The purpose of this study was to determine the correlations between inflammatory factors-including absolute lymphocyte count, lactate dehydrogenase, beta2-microglobulin, albumin, C-reactive protein, and ferritin-and the prognosis for survival in patients with multiple myeloma (MM) treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT). METHODS: Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. RESULTS: The median age of the 232 patients was 57 years (range, 33 to 77) and the male to female ratio was 1.09:1. In the multivariate analysis, fewer than two combined abnormal inflammatory factors was the only independent prognostic factor for superior progression-free survival (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 x 109/L and fewer than two combined abnormal inflammatory factors were independent prognostic factors for superior overall survival (RR, 4.739; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively). CONCLUSIONS: Patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed significantly shorter survival compared to those with fewer than two combined inflammatory factors. These results could be helpful for predicting prognosis in patients with MM.
Adult ; Aged ; Antineoplastic Agents/adverse effects/*therapeutic use ; Biomarkers, Tumor/*blood ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Hospitals, University ; Humans ; Induction Chemotherapy ; Inflammation Mediators/*blood ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multiple Myeloma/blood/diagnosis/*drug therapy/immunology/mortality ; Multivariate Analysis ; Neoadjuvant Therapy ; Odds Ratio ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation ; Thalidomide/adverse effects/*therapeutic use ; Time Factors ; Transplantation, Autologous ; Treatment Outcome

We evaluated the association of the APOE polymorphism with serum C-reactive protein levels and white blood cell count in two large population-based studies in Korean. The datasets included the Dong-gu study (n = 8,893) and the Namwon Study (n = 10,032). APOE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. Multivariable linear regression analysis was performed to evaluate the relationship of APOE genotypes with C-reactive protein levels and white blood cell count with adjustments for age, sex, body mass index, smoking, diabetes, hypertension, and serum lipids. In the multivariate model, carriers of E3E4 or E4E4 genotype had significantly lower C-reactive protein levels compared with carriers of E3E3 genotype group (0.50 mg/L vs. 0.67 mg/L; 0.37 mg/L vs. 0.67 mg/L, respectively, for the Dong-gu Study and 0.47 mg/L vs. 0.66 mg/L; 0.45 mg/L vs. 0.66 mg/L, respectively, for the Namwon Study). However, there was no difference in white blood cell count among APOE genotypes. We found that the APOE E4 allele is associated with lower C-reactive protein levels, but not white blood cell count. Our results suggest that APOE genotype may influence C-reactive protein levels through non-inflammatory pathway.
Aged ; Apolipoproteins E/*genetics ; C-Reactive Protein/*metabolism ; Female ; Genetic Association Studies ; Genotype ; Humans ; Inflammation/*blood/immunology ; Leukocyte Count ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide/genetics ; Prospective Studies ; Republic of Korea

OBJECTIVETo characterize the biological function of calmodulin (CaM) from Clonorchis sinensis (C. sinensis, Cs) and investigate its role in clonorchiasis-associated hepatic fibrosis.

METHODSThe full-length sequence of CsCaM gene was isolated from Cs cDNA library and its homologues were searched using BLASTx for comparison. Bioinformatics analysis was performed to compare the homologues and predict the physiochemical characteristics and functional domains. The gene was cloned in a prokaryotic plasmid and expressed in E. coli, and the recombinant protein was purified by affinity chromatography for immunizing rats to produce polyclonal antibodies, whose titer was determined using ELISA analysis. Immunoblotting analysis was carried out to determine of the purity and antibody recognition of CsCaM. Immunofluorescence assay was employed to analyze the tissue location of the protein. A rat model of liver fibrosis was established by introperitoneal injection of the recombinant protein.

RESULTSThe recombinant CsCaM protein obtained contained 150 amino acids with a theoretical molecular mass of 23.4 kD. CsCaM homologue had EF hand motifs. The recombinant pET-30a-CsCaM plasmid expressed in BL21 E. coli was about 23.4 kD. The total IgG antibody titer in the immunized mice reached the peak level (over 1: 51200) 2 to 4 weeks after the first injection. Immunohistochemistry showed that CsCaM located in the testis of adult C. sinensis. The rats receiving intraperitoneal injection of CsCaM showed severe liver inflammation with mild to moderate liver fibrosis.

CONCLUSIONThe pro-inflammation and pro-fibrosis effects of CsCaM in rat liver suggest its involvement in clonorchiasis- associated hepatic fibrosis.

Animals ; Antibodies, Helminth ; blood ; Antigens, Helminth ; immunology ; Calmodulin ; immunology ; Clonorchiasis ; immunology ; Clonorchis sinensis ; immunology ; Enzyme-Linked Immunosorbent Assay ; Gene Library ; Immunoglobulin G ; blood ; Inflammation ; Liver Cirrhosis ; parasitology ; Male ; Mice ; Rats ; Recombinant Proteins ; immunology

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