The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD), regulated renal mRNA and protein levels of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), OCT2, organic cation/carnitine transporter 1 (OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), and Caspase-1, resulting in the reduction of interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α (TNF-α) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Dipterocarpaceae ; chemistry ; Humans ; Hyperuricemia ; blood ; drug therapy ; immunology ; Interleukin-18 ; genetics ; immunology ; Interleukin-1beta ; genetics ; immunology ; Interleukin-6 ; genetics ; immunology ; Kidney ; drug effects ; immunology ; Male ; Mice ; Organic Anion Transport Protein 1 ; genetics ; immunology ; Plant Extracts ; administration & dosage ; Stilbenes ; administration & dosage ; Tumor Necrosis Factor-alpha ; genetics ; immunology ; Uric Acid ; blood

BACKGROUNDChronic obstructive pulmonary disease (COPD) is characterized by progressive loss of lung function and local and systemic inflammation, in which CD8+ T-cells are believed to play a key role. Activated CD8+ T-cells differentiate into distinct subpopulations, including interferon-γ (IFN-γ)-producing Tc1 and interleukin (IL)-17-producing Tc17 cells. Recent evidence indicates that Tc17 cells exhibit considerable plasticity and may convert into IL-17/IFN-γ-double producing (Tc17/IFN-γ) cells when driven by inflammatory conditions. The aim of this study was to investigate the Tc17/IFN-γ subpopulation in peripheral blood of patients with COPD and to evaluate their potential roles in this disease.

METHODSPeripheral blood samples were collected from 15 never-smokers, 23 smokers with normal lung function, and 25 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease 2-4). Proportions of the IL-17/IFN-γ-double expressing subpopulation were assessed using flow cytometry. Plasma concentrations of cytokines favoring Tc17/IFN-γ differentiation were measured by enzyme-linked immunosorbent assay.

RESULTSPatients with COPD had higher proportions of Tc17 cells and Tc17/IFN-γ cells in the peripheral blood than smokers and never-smokers. The plasticity of Tc17 cells was higher than that of Th17 cells. The percentages of Tc17 cells and Tc17/IFN-γ cells showed negative correlations with forced expiratory volume in 1 s % predicted value (r = -0.418, P = 0.03; r = -0.596, P = 0.002, respectively). The plasma concentrations of IL-6, transforming growth factor-β1, and IL-12 were significantly higher in patients with COPD compared with smokers and never-smokers.

CONCLUSIONSPeripheral Tc17 cells are increased and more likely to convert to Tc17/IFN-γ cells in COPD, suggesting that Tc17 cell plasticity may be involved in persistent inflammation of the disease.

Aged ; Female ; Forced Expiratory Volume ; Humans ; Interferon-gamma ; biosynthesis ; Interleukin-12 ; blood ; Interleukin-6 ; blood ; Lung ; physiopathology ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; immunology ; physiopathology ; Th17 Cells ; immunology

OBJECTIVETo analyze the characteristics of lymphocyte phenotypes in hepatitis B virus (HBV) transgenic mice and the effect of exogenous interferon-α on virological profiles and lymphocytes phenotypes of the mice.

METHODSHBV transgenic mice and wild-type (WT) mice were examined for serum levels of HBsAg, HBcAb, IL-21, and IL-6 using ELISA. The frequencies of CD4(+)T and CD19(+)B cells separated from the liver, spleen, and peripheral blood were detected by flow cytometry. Nine HBV transgenic mice were injected subcutaneously with recombinant mouse interferon alpha (rmIFN-α) and another 9 transgenic mice were injected with PBS, and their HBsAg, HBV DNA, IL-6, and IL-21 levels and frequencies of peripheral blood CD4(+)T and CD19(+)B cells were detected.

RESULTSHBV transgenic mice showed a high level of HBsAg with a detectable level of HBcAb and significantly increased serum levels of IL-21 and IL-6 as compared with WT mice (P<0.05). The transgenic mice had a significantly lower frequency of CD4(+) T cells in the peripheral blood, liver and spleen (P<0.05) but a significantly higher frequency of CD19(+) B cells in the liver (P<0.05). An inverse correlation between intrahepatic CD4(+) T cell frequency and serum HBsAg level while a positive correlation between intrahepatic CD19(+) B cell frequency and HBcAb level were found in HBV transgenic mice. Administration of rmIFN-α significantly increased the frequencies of CD4(+) T and CD19(+) B cells in the peripheral blood and the serum level of IL-6 in HBV transgenic mice (P<0.05).

CONCLUSIONHBV transgenic mice have lymphocyte subset dysregulation and exogenous interferon-α can modulate the immune function of the mice by regulating the frequencies of lymphocyte subsets.

Animals ; Antiviral Agents ; pharmacology ; B-Lymphocytes ; drug effects ; DNA, Viral ; blood ; Hepatitis B ; drug therapy ; immunology ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Interferon-alpha ; pharmacology ; Interleukin-6 ; blood ; Interleukins ; blood ; Liver ; immunology ; Lymphocyte Subsets ; cytology ; drug effects ; Mice ; Mice, Transgenic ; Phenotype ; T-Lymphocytes ; drug effects

PURPOSE: High mobility group box 1 (HMGB1) plays a central role in the pathogenesis of sepsis and multiple organ dysfunction syndromes. We investigated the associations of a single nucleotide polymorphism (SNP; rs1045411) in HMGB1 with various clinical parameters, severity, and prognosis in patients with sepsis, severe sepsis, or septic shock. MATERIALS AND METHODS: We enrolled 212 adult patients followed for 28 days. All patients were genotyped for rs1045411, and the serum levels of HMGB1 and several cytokines were measured. RESULTS: The proportions of patients according to genotype were GG (71.2%), GA (26.4%), and AA (2.4%). Among patients with chronic lung disease comorbidity, patients with a variant A allele had higher positive blood culture rates and higher levels of various cytokines [interleukin (IL)-1beta, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha] than those with the GG genotype. In the analysis of those with diabetes as a comorbidity, patients with a variant A allele had higher blood culture and Gram-negative culture rates than those with GG genotypes; these patients also had a higher levels of IL-17. In the analysis of those with sepsis caused by a respiratory tract infection, patients with a variant A allele had higher levels of IL-10 and IL-17 (all p<0.05). This polymorphism had no significant impact on patient survival. CONCLUSION: The variant A allele of rs1045411 appears to be associated with a more severe inflammatory response than the GG genotype under specific conditions.
Adult ; Aged ; Alleles ; Asian Continental Ancestry Group/genetics ; China/epidemiology ; Cytokines/*blood/*genetics ; Female ; Genotype ; HMGB1 Protein/blood/*genetics ; Humans ; Interleukin-10/genetics ; Interleukin-17/genetics ; Interleukin-6/blood ; Male ; Middle Aged ; Polymorphism, Genetic/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Prognosis ; Republic of Korea ; Sepsis/immunology/*metabolism/mortality ; Shock, Septic/immunology/*metabolism/mortality ; Survival ; Tumor Necrosis Factor-alpha/genetics

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.
Acute Disease ; Adult ; Alanine Transaminase/blood ; Biomarkers/blood ; Cytokines/*blood ; Enzyme-Linked Immunosorbent Assay ; Fas Ligand Protein/blood ; Female ; Hepatitis A/blood/virology ; Hepatitis A virus/*genetics/immunology ; Hepatitis B/blood/virology ; Hepatitis B virus/*genetics/immunology ; Humans ; Interleukin-6/blood ; Interleukin-8/blood ; Interleukins/blood ; Liver Failure/immunology/metabolism/*pathology ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic/immunology/*metabolism

Acute Disease ; C-Reactive Protein ; analysis ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Humans ; Interleukin-6 ; blood ; Ointments ; Pancreatitis ; drug therapy ; immunology

OBJECTIVETo explore the role of Th17 cells, CD4⁺ CD25⁺ regulatory Treg cells (Treg) and its transcription factor RORγt and FoxP3 in the pathogenesis of children with Henoch-Schonlein purpura (HSP) so as to provide a new strategy for treatment of children with Henoch-Schonlein purpura by regulating the balance of Th17 and Treg cells.

METHODSForty children with Henoch-Schonlein purpura in acute phase admitted in our hospital from February 2012 to March 2013 were enrolled in this study, forty healthy children were simultaneously used as controls. The expression of RORγt mRNA and FoxP3 mRNA in peripheral blood mononuclear cells was detected by real-time PCR using SYBR Green I. The levels of IL-17A, TGF-β1, IL-2 and IL-6 in serum were measured by ABC-ELISA. The ratio of Th17 cells to Treg cells in peripheral blood T lymphocytes was detected by flow cytometry.

RESULTSThe levels of Th17 cells (2.75 ± 0.60%) and RORγt mRNA (1.11 ± 0.51) in HSP group were significantly higher than levels of Th17 cells (1.41 ± 0.29%) and RORγt mRNA (0.65 ± 0.24) (P < 0.01) in control group, but the levels of Treg cells (4.56 ± 1.26%) and FoxP3 mRNA (1.15 ± 0.45) in HSP group were lower than those of Treg cells (7.85 ± 1.97%) and FoxP3 mRNA (2.32 ± 1.1) (P < 0.01) in the control group. The relative levels of serum IL-17A, IL-6, TGF-β1 (40.40 ± 11.81 pg/ml, 75.38 ± 27.19 pg/ml, 309.41 ± 81.03 pg/ml) in the HSP group were significantly higher than those in the control group [IL-17A (20.32 ± 10.70 pg/ml), IL-6 (25.16 ± 8.31 pg/ml), TGF-β1 (236.34 ± 66.01 pg/ml)] (P < 0.01), but the level of serum IL-2 (25.60 ± 13.19 pg/ml) in the HSP group was lower than that (34.42 ± 11.69 pg/ml) in the control group (P < 0.01). The further detection demonstrated that in the children with acute HSP, the expression of Th17 cells positively correlated with RORγt mRNA, IL-17A and IL-6 with the correlation coefficients of 0.887, 0.938 and 0.934 (P < 0.01), respectively. The positive correlation was also shown between the Treg cells and FoxP3 mRNA, IL-2 with the correlation coefficients of 0.834 and 0.932 (P < 0.01), respectively.

CONCLUSIONThere are higher expression levels of Th17 cells, RORγt mRNA and IL-17A, and lower expression levels of Treg cells, FoxP3 mRNA of children with HSP in acute phase, which shows that Th17/Treg imbalance exists in children with HSP in acute phase. The levels of serum IL-6, TGF-β1 increase and the serum IL-2 decrease in children with HSP in acute phase, moreover, there are the positive correlations between the levels of Th17 cells and expression of IL-6, as well as the level of Treg cells and expression of IL-2 in children with HSP in acute phase.

Case-Control Studies ; Child ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Humans ; Interleukin-17 ; blood ; Interleukin-2 ; blood ; Interleukin-6 ; blood ; Leukocytes, Mononuclear ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; Purpura, Schoenlein-Henoch ; immunology ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology ; Transforming Growth Factor beta1 ; blood

OBJECTIVETo investigate the effects of application of intermittent hemofiltration combined with hemoperfusion (HP) in the early stage of severe burn in the prevention and treatment of sepsis.

METHODSForty severely burned patients, admitted to our burn ward from June 2011 to March 2013, conforming to the study criteria, were divided into conventional treatment group (CT, n=20) and blood purification group (BP, n=20) according to the random number table. Patients in group CT received CT according to the accepted principles of treatment for a severe burn. Patients in group BP received CT and intermittent hemofiltration combined with HP once respectively on post injury day (PID) 3, 5, and 7, spanning 6 to 8 hours for each treatment. On PID 3, 5, 7, 10, and 14, body temperature, heart rate, and respiratory rate were recorded; white blood cell count (WBC), neutrophil granulocytes, blood urea nitrogen (BUN), and creatinine were determined; levels of IL-1, IL-6, TNF-α, and high-mobility group box 1 (HMGB1) in serum were determined by ELISA; level of LPS in serum was determined with the chromogenic substrate limulus amebocyte lysate method; level of procalcitonin (PCT) in serum was determined by double antibody sandwich immune chemiluminescence method. The symptoms and signs of sepsis were observed during the treatment. Data were processed with Fisher's exact test, chi-square test, analysis of variance for repeated measurement, and LSD-t test.

RESULTS(1) Except for that on PID 5, the mean body temperature of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.87 to 2.97, P values below 0.05). The heart rate was significantly slower in patients of group BP than in group CT from PID 3 to 14 (with t values from 1.78 to 3.59, P values below 0.05). Except for that on PID 3, the respiratory rate of patients in group BP was significantly slower than that of group CT at each of the rest time points (with t values from 1.93 to 2.85, P values below 0.05). (2) The levels of WBC, neutrophil granulocytes, BUN, and creatinine of patients in group BP were significantly lower than those of group CT (with t values from 1.78 to 4.23, P values below 0.05). (3) Except for that on PID 3, the level of IL-1 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.97 to 4.16, P values below 0.05). Except for that on PID 7, the level of IL-6 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 2.11 to 6.34, P values below 0.05). The levels of TNF-α and HMGB1 of patients in group BP were significantly lower than those of group CT from PID 3 to 14 (with t values from 1.98 to 5.29, P values below 0.05). (4) On PID 3, 5, 7, 10, and 14, the levels of LPS and PCT of patients in group BP were respectively (0.23 ± 0.07), (0.27 ± 0.09), (0.22 ± 0.06), (0.20 ± 0.08), (0.15 ± 0.07) EU/mL, and (0.44 ± 0.12), (0.67 ± 0.13), (0.74 ± 0.13), (0.64 ± 0.12), (0.71 ± 0.10) ng/mL, and they were lower than those of group CT [(0.37 ± 0.08), (0.45 ± 0.09), (0.56 ± 0.09), (0.48 ± 0.08), (0.40 ± 0.08) EU/mL, and (0.74 ± 0.11), (1.16 ± 0.12), (1.40 ± 0.13), (1.55 ± 0.15), (1.49 ± 0.14) ng/mL, with t values from 1.88 to 3.43, P values below 0.05]. (5) The incidence of sepsis of patients in group BP was obviously lower than that of group CT (χ² = 6.94, P<0.01).

CONCLUSIONSIntermittent hemofiltration combined with HP can effectively improve blood biochemical indexes and vital signs and reduce the occurrence of burn sepsis by decreasing the levels of proinflammatory cytokines, LPS, and PCT.

Biomarkers ; blood ; Burns ; blood ; complications ; immunology ; therapy ; Calcitonin ; Calcitonin Gene-Related Peptide ; Cytokines ; blood ; HMGB1 Protein ; Hemofiltration ; methods ; Hemoperfusion ; methods ; Humans ; Interleukin-1 ; blood ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Protein Precursors ; Sepsis ; blood ; immunology ; prevention & control ; therapy ; Serum ; Severity of Illness Index ; Treatment Outcome ; Tumor Necrosis Factor-alpha

OBJECTIVETo investigate the levels of cytokines related to T-helper (Th) 17 cells in serum and signal transducers in the psoriatic lesions of patients with psoriasis vulgaris of blood-heat syndrome (BHS) and blood-stasis syndrome (BSS).

METHODSSixty patients with psoriasis vulgaris were divided into the BHS and BSS groups according to the syndrome differentiation of Chinese medicine (CM). Ten healthy subjects were considered as the control group. Cytokine levels of interleukin (IL)-17, IL-23 and IL-6 in serum were determined by enzyme-linked immunosorbent assay. Expression levels of signal transducer and activator of transcription 3 (STAT3), p38-mitogen-activated protein kinase (MAPK) and STAT6 in the psoriatic lesions were determined using immunohistochemistry (IHC), Western blot, and real-time quantitative reverse transcription polymerase chain reaction, respectively.

RESULTSProduction of IL-17, IL-23 and IL-6 in the BHS group and BSS group were significantly increased compared with those in the control group (P<0.05). Levels of IL-17 and IL-23 in the BHS group were higher than those in the BSS group (P<0.05). Compared with the control group, IHC positive expressions and protein expressions of STAT3 and p38-MAPK, and the STAT3 mRNA expressions in the BHS and BSS groups were significantly higher (P<0.05 or P<0.01). The protein expression of STAT3 in the BHS group was significantly higher than that in the BSS group (P<0.05).

CONCLUSIONSCytokines in serum and signal transducers in the psoriatic lesions alter with various CM syndromes of psoriasis. The results provide scientific basis for the treatment based on syndrome differentiation of CM in treating psoriasis vulgaris.

Adult ; Female ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Interleukin-17 ; blood ; Interleukin-23 ; blood ; Interleukin-6 ; blood ; Male ; Psoriasis ; blood ; enzymology ; genetics ; immunology ; RNA, Messenger ; genetics ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; STAT6 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Syndrome ; Th17 Cells ; immunology ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

BACKGROUNDIncreasing evidence supports an association between periodontitis and systemic diseases. Leptin is involved both in the energy metabolism and inflammatory processes and is suggested to be a link between periodontal infection and systemic health. The present study aimed to evaluate the peripheral leptin concentration in patients with aggressive periodontitis (AgP) and to explore the relationship between leptin and systemic inflammation.

METHODSNinety patients with AgP visiting the Clinic of the Periodontology Department, Peking University School and Hospital of Stomatology between July 2001 and May 2006, and 44 healthy controls (staff and student volunteers in the same institute) were recruited. Plasma levels of leptin and inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay. Correlation and multiple linear regression analysis were performed to analyze the association between plasma leptin level and other variables.

RESULTSPlasma leptin level of AgP group was significantly higher than that of the control group (19.7 ± 4.4 ng/ml vs. 7.5 ± 1.3 ng/ml, P < 0.01). After controlling for age, gender, and body mass index, positive correlation was observed between plasma leptin concentration and log-transformed levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and CRP), and the partial correlation coefficients ranged from 0.199 to 0.376 (P < 0.05). Log-transformed IL-1β and IL-6 levels entered the final regression model (standardized β were 0.422 and 0.461 respectively, P < 0.01).

CONCLUSIONSElevated plasma leptin concentration may be associated with increased systemic levels of inflammatory markers in AgP patients.

Adolescent ; Adult ; Aggressive Periodontitis ; blood ; immunology ; C-Reactive Protein ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; blood ; Leptin ; blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; blood ; Young Adult