Aging is associated with altered immune responses including dysregulation of cytokine production. Of cytokines, interleukin-1 (IL-1) family has been primarily involved with central nervous system. To evaluate the age-related different response of IL-1 family following peripheral administration of lipopolysaccharide (LPS), immunohistochemical study of IL-1beta and IL-1 receptor expression was performed on Sprague-Dawley rat brain. Experimental animals were divided into four groups; saline-treated young (3-5 months) and old (over 24 months), and LPS-treated young and old groups. After intraperitoneal (i.p.) injection of LPS, three to five rats within each group were killed at 1, 2, 4, 8 and 16 hr. After fixation in 4% neutral buffered formalin, the brain slices were paraffin-embedded. Immunohistochemical staining using labelled streptavidin biotin was performed. The results showed that IL-1beta immunoreactivity was seen in the endothelial cell of pons in both LPS-reated young and old rats, with slightly longer persistency in old group. IL-1RI immunoreactivity appeared initially in the neurons of cerebral cortex in LPS-treated old group, compared with predominantly the cerebellum in LPS-treated young group. In conclusion, our study shows that there is age-related, different neuronal localization of IL-1RI expression at different points of time after LPS treatment.
Age Factors ; Animal ; Brain Chemistry/drug effects* ; Gene Expression Regulation/drug effects ; Immunohistochemistry ; Interleukin-1/genetics ; Interleukin-1/analysis* ; Lipopolysaccharides/toxicity* ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Interleukin-1/analysis

Blood Cell Count ; Bone Marrow Cells ; pathology ; Child ; Cytokines ; analysis ; Fever ; Histiocytosis, Non-Langerhans-Cell ; metabolism ; pathology ; therapy ; Humans ; Interleukin-2 ; analysis ; Interleukin-6 ; analysis ; Receptors, Interleukin-1 ; analysis

BACKGROUNDTriggering receptors expressed on myeloid cells (TREM) proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clinical significance of soluble TREM-1 (sTREM-1) in pleural effusions, and to determine the effects of pneumonia on pleural sTREM-1 concentrations.

METHODSPleural fluid was collected from 109 patients who presented to the respiratory institute (35 with malignant pleural effusion, 31 with tuberculous pleural effusion, 21 with bacterial pleural effusion, and 22 with transudate). The concentrations of sTREM-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined in effusion and serum samples by enzyme linked immunosorbent assay (ELISA).

RESULTSThe concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups (all P < 0.001). An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86% and a specificity of 93%. Pleural sTREM-1 levels were positively correlated with levels of TNF-alpha and IL-1beta. Patients with complicating bacterial pneumonia did not have elevated concentration of sTREM-1 in pleural effusion when compared with patients without pneumonia.

CONCLUSIONSDetermination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies. The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Humans ; Interleukin-1beta ; analysis ; Membrane Glycoproteins ; analysis ; Middle Aged ; Pleural Effusion ; diagnosis ; metabolism ; Pneumonia ; metabolism ; Prospective Studies ; Receptors, Immunologic ; analysis ; Triggering Receptor Expressed on Myeloid Cells-1 ; Tumor Necrosis Factor-alpha ; analysis

BACKGROUND: The human immune response to Mycobacterium tuberculosis is mediated by macrophages and T-lymphocytes. The alveolar macrophage phagocyting mycobacterium produces interleukin (IL) -1 as an inflammatory mediator, and IL-8 as a cytokine for leukocyte recruitment and granuloma formation. Interleukin-1 receptor antagonist (IL-1ra) is an internal antagonist of IL-1. METHODS: Plasma levels of IL-1ra and IL-8 and other serologic markers were measured in 18 patients with active tuberculosis before treatment and after 2 months and 6 months of treatment. RESULTS: During treatment with antituberculous medication, patients showed significant changes in hemoglobin, hematocrit, white blood cells (WBC), platelet, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin and plasma IL-1ra. After 2 months of treatment, ESR and CRP diminished significantly; after 6 months, hemoglobin increased while WBC, platelet, ESR, CRP and ferritin decreased significantly compared to their pre-treatment levels. There were two groups: patients with delayed therapeutic responses, and patients with early responses. At each point of observation, the former group of patients showed lower body weight and lower levels of hemoglobin and hematocrit, and higher levels of WBC, platelet, ESR, IL-8 and IL-1ra than the latter group. During the course of the treatment, we observed considerable differences in body weight, body mass index, hemoglobin, hematocrit, WBC and platelet counts, ESR, CRP and ferritin in both the early-response and delayed-response groups. CONCLUSION: We believe that the plasma concentrations of IL-1ra and IL-8, which showed different peaks during the course of treatment, reflected their different functions and patterns of secretion. Moreover the concentrations did not seem as sensitive as other inflammatory markers to evaluate disease activity during antituberculosis treatment. However, IL-1ra can be considered a marker for disease activity and response to treatment.
Adult ; Aged ; Aged, 80 and over ; Antitubercular Agents/therapeutic use ; Biological Markers/*blood ; C-Reactive Protein/analysis ; Comparative Study ; Female ; Human ; Interleukin-8/*blood ; Male ; Middle Aged ; Receptors, Interleukin-1/*antagonists & inhibitors ; Sialoglycoproteins/*blood ; Tuberculosis, Pulmonary/*blood/*drug therapy

Interleukin-1 receptor antagonist (IL-1ra), tumor necrosis factor soluble receptors (sTNF-R) type I and II, and regulated upon activation, normal T-cell expressed and secreted (RANTES) play an important role in the modulation of primary glomerulonephritis (GN) course. The aim of the study was to assess whether pre-treatment measurements of IL-1ra, sTNF-R, and RANTES assessed conjointly may be useful as predicting factors in patients with GN. In 84 patients (45 males and 39 female) serum concentration (pg/mL) and urinary excretion (pg/mgCr) of cytokines were measured. After 12 months of therapy with steroids and cyclophosphamide the patients were divided into two subgroups: Responders (R) and Non-Responders (NR) according to the treatment results. The urinary IL-1ra, TNF-RI and RII were significantly higher in R than NR (1,732 vs 646 with P < 0.001, 13.1 vs 6.3 with P = 0.005, and 33.6 vs 14.4 with P = 0.012). The urinary RANTES excretion was increased in NR (79.6 vs 28.5; P < 0.001). The multivariable analysis showed that if conjointly assessed, only urinary IL-1ra, TNF-R I and R II, RANTES with 85% probability pointed the feature remission (R). In conclusion, the urinary excretion of IL-1ra, TNF-R I and R II, and RANTES examined conjointly are effective in predicting favorable response to immunosuppressive treatment in patients with GN.
Adult ; Cyclophosphamide/therapeutic use ; Female ; Glomerulonephritis/drug therapy/*metabolism/pathology ; Humans ; Immunosuppressive Agents/therapeutic use ; Interleukin 1 Receptor Antagonist Protein/*analysis/blood/urine ; Lymphocyte Activation ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Receptors, Tumor Necrosis Factor, Type I/*analysis/blood/urine ; Receptors, Tumor Necrosis Factor, Type II/*analysis/blood/urine ; Steroids/therapeutic use ; T-Lymphocytes/immunology/metabolism

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

BACKGROUND/AIMS: Several epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group. METHODS: Patients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin 1β (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor α (TNFA) genes of patients with AP were compared to those of normal controls. RESULTS: Between January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN −1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (−118C>T, c47+242C>T, +3954C/T, and −598T>C) and TNFA (−1211T>C, −1043C>A, −1037C>T, −488G>A, and −418G>A). CONCLUSIONS: IL1RN −1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.
Asian Continental Ancestry Group ; DNA ; Epidemiologic Studies ; Ethnic Groups* ; Genotype ; Humans ; Interleukins ; Introns ; Pancreatitis* ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Prospective Studies ; Receptors, Interleukin-1 ; Sequence Analysis, DNA ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the effect of chronic treatment of enbrel (EB), a TNF-alpha antagonist, in a well defined congestive heart failure (CHF) rat model and test the hypothesis that chronic treatment of EB in CHF rats may limit the progression of Left ventricular (LV) dysfunction and structure remodeling and decrease cardiac IL-1beta levels.

METHODSWe measured cardiac conformation, contractile performance and cytokines level in 8 age-matched normal adult rats (control group) and 8 rats with isoproterenol (ISO)-induced Heart failure (ISO group) and 8 rats with ISO-induced lesion but received EB treatment (EB group).

RESULTSLV end diastolic diameter and LV end systolic diameter in EB group were significantly less and LV fractional shortening was significantly larger than ISO group (9.2 +/- 0.3 mm vs 9.5 +/- 0.2 mm, 5.8 +/- 0.5 mm vs 6.5 +/- 0.3 mm, 0.37 +/- 0.03 vs 0.31 +/- 0.02, P < 0.05, P < 0.01, P < 0.01 respectively , but there was no significant difference of LV posterior wall thickness at end diastole between the two groups; LV end systolic pressure (P(ES)) dp/dt(max) in EB group were significantly greater than ISO group (104.8 +/- 4.6 mm Hg vs 98.4 +/- 4.9 mm Hg, 8395 +/- 940 mm Hg/s vs 6898 +/- 612 mm Hg, P < 0.05 P < 0.01 respectively), and LV end diastolic pressure (P(ED)) dp/dt(min), time constant of LV relaxation were significantly lower than ISO group (3.8 +/- 0.6 mm Hg vs 7.1 +/- 0.8 mm Hg, -5963 +/- 475 mm Hg/s vs-5030 +/- 316 mm Hg/s,15.4 +/- 0.8 ms vs 21.3 +/- 1.4 ms, P < 0.01, respectively . Although cardiac contractile performance in the EB group was greatly improved, there still was a big gap when compared with the control group. The ratio of LV weight to body weight in the EB group was significantly higher than control group 2.82 +/- 0.07 mg/g vs 2.28 +/- 0.08 mg/g, P < 0.01 but there was no significant difference when compared with the ISO group. There was no significant difference between the serum level of TNF-alpha in EB group and ISO group the it could not be detected in control group. TNF-alpha levels in LV of EB group was significantly higher than control group, 757.6 +/- 46.8 pg/g vs 367.5 +/- 22.7 pg/g, P < 0.01 but there was no significant difference when compared with ISO group. The IL-1beta level in LV of EB group was significantly lower than ISO group 356.2 +/- 28.5 pg/g vs 518.4 +/- 32.5 pg/g, P < 0.05 and it could not be detected in control group. The serum level of IL-1beta could not be detected in any rats.

CONCLUSIONEB administered as soon as possible when ISO induced myocardial necrosis occurs can greatly improve cardiac contraction, and the improvement may be partly due to a decrease in the IL-1beta level in LV, besides the direct blocking effect of EB on TNF-alpha. EB can alleviate cardiac remodeling by its effect on LVEDD.

Animals ; Body Weight ; drug effects ; Echocardiography ; Etanercept ; Heart Failure ; diagnostic imaging ; drug therapy ; physiopathology ; Immunoglobulin G ; therapeutic use ; Interleukin-1 ; analysis ; Isoproterenol ; pharmacology ; Male ; Rats ; Rats, Wistar ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Tumor Necrosis Factor-alpha ; analysis ; antagonists & inhibitors ; Ventricular Dysfunction, Left ; prevention & control

BACKGROUNDT cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules.

METHODSThe ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n = 6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-gamma and interleukin-4 producing cells among splenic CD4(+) lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR.

RESULTSTreatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Also, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb) group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group.

CONCLUSIONThe results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor (TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.

Adenine Nucleotide Translocator 1 ; immunology ; Animals ; Antibodies, Monoclonal ; therapeutic use ; Autoantibodies ; blood ; Autoimmune Diseases ; therapy ; CD4 Antigens ; immunology ; Cardiomyopathy, Dilated ; immunology ; therapy ; Interferon-gamma ; biosynthesis ; Interleukin-4 ; biosynthesis ; Leukocyte Common Antigens ; analysis ; Mice ; Mice, Inbred BALB C ; Receptors, Antigen, T-Cell ; antagonists & inhibitors ; physiology ; Signal Transduction

OBJECTIVETo investigate the spectrum of β -thalassemia mutations in Guizhou Province.

METHODSFor 542 individuals suspected to have β -thalassemia by decreased mean corpuscular volume (MCV) and corpuscle hemoglobin (MCH) by routine blood test and hemoglobin electrophoresis, reverse dot blot hybridization (RDB) was performed to detect 17 known β -thalassemia mutations, including 8 common and 9 rare mutations. For cases where no mutation was identified, the entire human β -globin gene was screened to find other rare mutations. The distribution and frequencies of detected β -thalassemia mutations were then analyzed.

RESULTSA total of 460 individuals were diagnosed as β -thalassemia by DNA analysis, which included 352 heterozygotes, 67 compound heterozygotes and 41 mutant homozygotes. A total of 12 β -thalassemia mutations were detected in these individuals. The mutations have ranked from high to low frequency as: CD17 (40.74%), CD41-42 (33.69%), IVS-II-654 (13.76%), -28 (3.70%), β E (3.35%), CD71-72(1.94%), CD43 (1.06%), IVS-I-1 (0.71%), CD27-28 (0.35%), -29(0.35%), CAP (0.18%), and CD121 (0.18%). The former six mutations have accounted for 97.18% of all. CD121 (GAA> TAA) detected from a heterozygote, as a dominant mutation, has been firstly found in the Chinese population.

CONCLUSIONThe spectrum of β -thalassemia in Guizhou Province showed certain distinct characteristics, with CD17 being the most common mutation. The newly discovered mutation of CD121 has expanded the spectrum of β -thalassemia in Chinese population. Our result may provide valuable information for the prevention and control of β -thalassemia in Guizhou.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; China ; DNA Mutational Analysis ; Female ; Humans ; Infant ; Leukosialin ; genetics ; Male ; Middle Aged ; Mutation ; Platelet Membrane Glycoprotein IIb ; genetics ; Receptors, Interleukin-1 Type I ; genetics ; Young Adult ; beta-Globins ; genetics ; beta-Thalassemia ; diagnosis ; ethnology ; genetics