OBJECTIVETo investigate the effects of Modified Sanhuang Decoction (, MSD) enema on the serum tumor necrosis factor alpha (TNF-α) and colonic mucosa interleukin-1β (IL-1β), interleukin-6 (IL-6) levels in experimental ulcerative colitis (UC) rats.

METHODSForty-five male Wistar rats were randomly divided into 4 groups: normal group (n=12), model group (n=11), salazosulfapyridine (SASP) group (n=11) and MSD group (n=11). The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Rats in the normal group and model group were clystered with 0.9% normal saline, while in the SASP group and MSD group were clystered with SASP and MSD enema, respectively. After drug administration (10 mL/kg body weight, for 7 days), colonic gross changes and colonic mucosa histology were observed, serum TNF-α and colonic mucosa IL-1β, IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay, respectively.

RESULTSAs compared with the normal group, the experimental UC rats, the colonic mucosal damage index scores (CMDIs), histopathological scores (HS) and the serum TNF-α and colonic mucosa IL-1β, IL-6 levels significantly increased (P<0.05 or P<0.01). In the MSD and SASP groups, the ulcer area significantly reduced, and edema disappeared. The CMDIs, HS, the serum TNF-α and colonic mucosa IL-1β, IL-6 levels in the MSD and SASP groups significantly decreased (P<0.05 or P<0.01) compared with the model group. The CMDIs in the MSD group were lower than that in the SASP group (P<0.05), but there were no significant differences in HS, serum TNF-α or colonic mucosa IL-1β, IL-6 levels between the MSD and SASP groups.

CONCLUSIONMSD enema can improve colonic mucosa impairment and decrease serum TNF-α and colonic mucosa IL-1β, IL-6 levels in experimental UC.

Animals ; Colitis, Ulcerative ; metabolism ; therapy ; Colon ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Enema ; Interleukin-1beta ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Intestinal Mucosa ; metabolism ; Male ; Rats ; Rats, Wistar

OBJECTIVETo observe the effect of Tetramethyl pyrazine (TMP) on the cytokines and inflammatory mediators in the serum and the synovial fluid of collagen-induced arthritis (CIA)rats, and further to investigate its possible mechanisms for treating rheumatoid arthritis (RA).

METHODSType II CIA rat model was established. Rats in the TMP group were administered with TMP at 50 mg/kg and 100 mg/kg, once daily. Dexamethasone at 2.0 mg/kg was intramuscularly injected to those in the Dexamethasone treated group, once daily. Normal saline at 2 mL/kg was given to those in the normal control group and the model group, once daily. All medication was started from the 7th day, lasting to the 35th day. CIA rats' foot swelling degree was observed. Contents of serum IL-1, IL-6, IL-2, NO and PGE2in the synovial fluid were detected by radioimmunoassay and nitrate reduction method.

RESULTSCompared with the normal group, the foot swelling obviously increased, contents of NO and PGE2 in the synovial fluid were obviously elevated in the model group (P < 0.01). Compared with the model group, the foot swelling could be obviously inhibited by 100 mg/kg TMP and Dexamethasone; serum levels of IL-1 and IL-6 obviously decreased, serum IL-2 level obviously increased, contents of NO and PGE, decreased (P < 0.01). TMP 50 mg/kg could obviously inhibit the foot swelling of CIA rats (P < 0.01). There was no statistical difference in other indices (P > 0.05).

CONCLUSIONSTMP at 100 mg/kg showed obvious inhibition on CIA rats. Its inhibitory effect might be correlated to inhibiting activities of endogenous cytokines and the generation of inflammatory mediators in inflammation local regions, improving contents of anti-inflammation cytokines, and inducing the balance of the inflammatory cytokine network.

Animals ; Arthritis, Experimental ; blood ; metabolism ; Dinoprostone ; metabolism ; Female ; Interleukin-1beta ; blood ; Interleukin-2 ; blood ; Interleukin-6 ; blood ; Male ; Nitric Oxide ; metabolism ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Synovial Fluid ; metabolism

OBJECTIVETo investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats.

METHODSThe I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R.

RESULTSIn the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05).

CONCLUSIONGinsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.

Animals ; Brain ; metabolism ; Brain Ischemia ; blood ; metabolism ; Ginsenosides ; administration & dosage ; pharmacology ; Interleukin-1beta ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; metabolism

This study was purposed to explore the significance of tissue factor (TF), tissue factor pathway inhibitor (IFPI) and interleukin-1beta (IL-1beta) in the evaluation of development, curative effect and prognosis of AL patients. ELISA was used to detect the levels of TF, TFPI and IL-1beta in plasma of 20 healthy individuals and 24 newly diagnosed AL patients. All the three indications of patients were measured in different stages including pre-chemotherapy phase, at 72 hours after chemotherapy, complete remission phase. The results showed that as compared with normal control, levels of TF, TFPI and IL-1beta in plasma of AL patients during pre-chemotherapy phase were higher (p < 0.01); as compared with pre-chemotherapy phase, levels of TF, IL-1beta were elevated at 72 hours after -chemotherapy (p < 0.05). However, the levels of TFPI was much lower than that of 72 hours after chemotherapy (p < 0.01). 16 out of 24 patients got complete remission, there was no difference of TF, TFPI and IL-1beta between complete remission group and normal control group. It is concluded that the levels of TF, TFPI and IL-1beta in plasma can be used as the indicators for understanding clinical features, evaluating disease status and predicting prognosis in acute leukemia patients.
Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Child ; Female ; Humans ; Interleukin-1beta ; blood ; Leukemia ; blood ; Lipoproteins ; blood ; Male ; Middle Aged ; Thromboplastin ; metabolism ; Young Adult

OBJECTIVETo determine the level of high-density lipoprotein cholesterol (HDL-C), serum C-reactive protein (CRP) and inflammation cytokines and investigate the concentration between periodontal disease and coronary heart disease (CHD).

METHODSSixty-six patients with CHD and chronic periodontitis [(C+P) group], forty-four with only CHD (C group), fifty-six with only chronic periodontitis (C group), and forty-three healthy controls (H group) were included in this study. The diagnosis of chronic periodontitis and CHD was based on accepted clinical criteria. Serum levels of HDL-C, CRP, IL-6, tumor necrosis factor (TNF)-alpha and IL-1beta were tested in all patients and controls.

RESULTSThe periodontal conditions of these four groups were significantly different (P<0.05). The clinical periodontal parameters [probing depth (PD), attachment loss (AL), and bleeding on probing (BOP)] in patients with (C+P) group, P group, C group and H group were [(4.55+/-0.85) mm, (3.78+/-0.34) mm, 69.6%], [(4.06+/-0.61) mm, (3.05+/-0.44) mm, 63.6%], [(1.85+/-0.67) mm, (1.26+/-0.39) mm, 20.5%], [(1.12+/-0.33) mm, (0.42+/-0.83) mm, 4.6%], respectively. The levels of HDL-C in H group, C group, P group and (C+P) group were (1.42+/-0.21), (1.22+/-0.18), (1.24+/-0.21) and (1.04+/-0.22) mmol/L, respectively. T compare with other three groups, the level of HDL-C in (C+P) group is the lowest. The levels of CRP, IL-6, TNF-alpha and IL-1beta in (C+P) group were significantly higher than other groups (P<0.05).

CONCLUSIONSHDL-C, CRP, IL-6, TNF-alpha and IL-1beta may be associated with the pathogenesis of periodontitis and CHD. There may be a relationship between the two diseases.

C-Reactive Protein ; metabolism ; Cholesterol, HDL ; blood ; Chronic Periodontitis ; blood ; complications ; pathology ; Coronary Disease ; blood ; complications ; Female ; Humans ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Male ; Middle Aged ; Periodontal Attachment Loss ; blood ; Periodontal Index ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVE: To investigate the role of P53 and high mobility group protein 1 (HMGB1) protein expression in liver fibrosis stages in chronic hepatitis B patients.
 METHODS: According to the pathological grades, 103 patients were divided into 3 groups: no fibrosis group (n=18), low fibrosis group (n=49) or high fibrosis group (n=36). Serum HMGB1 levels were determined and receiver operating characteristic (ROC) curve was made based on the HMGB1 level and liver fibrosis score. Liver fibrosis model was developed by CCl4 in 60 male SD rats, which were sacrificed 6 or 12 weeks later. The degree of fibrosis was examined by Masson staining; HMGB1 and P53 protein expression were analyzed by Western blot; histone deacetylase (HDAC) activity, TNF-α, IL-1β and IL-6 levels in serum were measured.
 RESULTS: The serum levels of HMGB1 level in low and high fibrosis groups were significantly higher than that in no fibrosis group (P<0.01, respectively). ROC curve showed that serum HMGB1 in the diagnosis of hepatic fibrosis with cut off at 74 pg/mL, specificity at 65% and sensitivity at 87%. Compared with the control group, HMGB1 expression in both low and high fibrosis group was decreased in nucleus but was increased in cytoplasm, accompanied by the elevated P53 expression, increased HDAC activity and inflammatory cytokine levels (all P<0.01, respectively).
 CONCLUSION P53 and HMGB1 expression was significantly increased in chronic hepatitis B patients with liver fibrosis; serum HMGB1 level was positively correlated with the degree of liver cirrhosis and HMGB1 could be used as a sensitive and specific index for liver fibrosis prognosis.
Animals ; HMGB1 Protein ; metabolism ; Hepatitis B, Chronic ; metabolism ; pathology ; Humans ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVEInflammation serves as the initial pathologic step of cardiovascular diseases including atherosclerosis. Resveratrol possesses many pharmacological properties including antioxidant, cardioprotective and anti-cancer effects. In this study, we investigate the anti-inflammatory effect and mechanisms of resveratrol in an atherosclerotic rabbit model.

METHODSRabbit were assigned to six groups (n = 10 each): control, high fat diet group, resveratrol low, medium and high dose groups, resveratrol pretreatment group. The serum tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were analyzed by Enzyme-linked immuno sorbent assay(ELISA). Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades and NF-κB were determined by Western blot.

RESULTSCompared with the control group, the expression of serum inflammatory factors IL-1β, IL-6, TNF-α were increased in high-fat group (all P < 0.05). Compared with high-fat group, the expressions of IL-6, IL-1β, TNF-α were significantly reduced in resveratrol low, medium, high dose groups and resveratrol pretreatment group (all P < 0.01), and this effect is dose-dependent. In addition, the NF-κB, p38MAPK, JNK, ERK1/2 protein phosphorylation in high-fat group were significantly upregulated compared with control group (P < 0.05), which (except ERK1/2 phosphorylation level) were significantly downregulated in resveratrol treatment group and resveratrol pretreatment group.

CONCLUSIONThis study indicates that resveratrol reduces serum inflammatory cytokines in this atherosclerotic rabbit model via down-regulation phosphorylation of NF-κB, and MAPKs signaling, which might serve as the anti-inflammatory molecular basis of resveratrol.

Animals ; Atherosclerosis ; drug therapy ; metabolism ; Disease Models, Animal ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Male ; Mitogen-Activated Protein Kinases ; metabolism ; NF-kappa B ; metabolism ; Phosphorylation ; Rabbits ; Signal Transduction ; drug effects ; Stilbenes ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

BACKGROUNDAcute lymphoblastic leukemia (ALL) and chemotherapy can cause immune imbalance, and gaseous molecule hydrogen sulfide (H2S) can participate in the process of immune response. This study aimed to investigate the immune regulation of H2S in pediatric ALL.

METHODSChildren (n = 78) with ALL admitted during 2010-2013 were included in this study. Two blood samples were collected in period of before chemotherapy, bone marrow remission and two days after chemotherapy, respectively. Serum contents of H2S and cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10) and macrophage inflammatory protein-1α (MIP-1α), were detected using ELISA method. Stepwise regression was used to analyze the correlation between H2S and cytokines. Furthermore, human Jurkat cells were cultured in vitro, and nucleoprotein of Jurkat cells and peripheral blood mononuclear cells (PBMCs) were collected, contents of cystathionine γ-lyase (CSE) and certain cytokines were measured by Western blotting.

RESULTSSerum concentrations of H2S, IL-1β, IL-6, IL-10 and MIP-1a in children with ALL were increased significantly (P < 0.01), while concentrations of IL-2, TNF-α, IFN-γ and IL-4 decreased obviously (P < 0.01). In patients after chemotherapy, concentrations of H2S and IL-10 were decreased significantly (P < 0.05), but IL-4 and IFN-γ concentrations increased markedly (P < 0.05). At remission stage, H2S, IL-1β, IL-4, IL-6, IL-10 and MIP-1α concentrations were further decreased markedly (P < 0.05), but concentrations of IL-2, TNF-α and IFN-γ increased again (P < 0.05). Protein contents of CSE, IL-10, IL-4 and IL-2 of PBMCs also increased markedly in children with ALL. Moreover, changes of CSE protein contents of PBMCs were consistent with serum H2S contents, and there were significant correlation between H2S and certain cytokines based on stepwise regression analysis. Furthermore, compared with those of PBMCs group, in vitro study indicated that Jurkat cells of H2S group expressed IFN-γ, IL-10, IL-4 and IL-2 protein increased obviously (P < 0.05), while IL-4, IL-2 and CSE expression of PPG group decreased markedly (P < 0.05).

CONCLUSIONGaseous molecule H2S might participate in the process of immune regulation in pediatric ALL through modulating transcription and expression of cytokines.

Child ; Child, Preschool ; Cystathionine gamma-Lyase ; blood ; Female ; Humans ; Hydrogen Sulfide ; blood ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-1beta ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Leukocytes, Mononuclear ; metabolism ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the protective effect of amrinone against experimental lung ischemia /reperfusion (I/R) injury.

METHODSTwenty-four Sprague-Dawley rats were randomly divided into 3 groups (n=8 each): sham- operated group, I/R group, and amrinone-treated I/R group (AMR group). The left lung of rats was subjected to ischemia for 90 minutes, followed by reperfusion for 2 hrs, to induce an I/R lung injury model. The rats of the AMR group received amrinone (10 mg/kg) intravenously 30 minutes before ischemia and 5 minutes before reperfusion. After 2 hrs of reperfusion, carotid artery blood was collected for blood-gas analysis and detection of serum levels of IL-1beta, IL-8 and TNF-alpha. The left lung was removed for detection of the lung wet/dry ratio, the erythrocuprein (SOD) activity and the malonaldehyde (MDA) content as well as the pathological changes.

RESULTSAfter 2 hrs of reperfusion, there were no significant differences in artery partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2) among the three groups. The lung wet/dry ratio (5.3 +/- 0.5 vs 4.8 +/- 0.1) and the MDA content (0.66 +/- 0.16 nmol/mg prot vs 0.47 +/- 0.06 nmol/mg prot) in the I/R group were significantly higher than those of the sham-operated group (P <0.05). The administration of amrinone markedly reduced the lung wet/dry ratio (4.8 +/- 0.2) and the MDA content (0.51 +/- 0.09 nmol/mg prot) and increased the SOD activity (54.7 +/- 6.8 vs 39.3 +/- 3.0 U/mg prot) when comparing the I/R group (P < 0.05). The serum levels of IL-1beta, IL-8 and TNF-alpha in the I/R group were 22.08 +/- 3.85, 21.92 +/- 5.56 and 30.50 +/- 3.77 pg/mL respectively, which were significantly higher than those of the sham-operated group. The AMR group showed lower serum levels of IL-1beta, IL-8 and TNF-alpha (16.66 +/- 3.02,14.73 +/- 2.75 and 22.48 +/- 3.82 pg/mL, respectively) compared with the I/R group (P < 0.01). The pathologic examination displayed that the lung tissue structure was normal and there was no hyperemia in the sham-operated and the AMR groups. The lung tissue structure of the I/R group was nearly normal but there were hyperemia and more inflammatory cells than the sham-operated and the AMR groups.

CONCLUSIONSAmrinone has protections against lung I/R injury, possibly through its anti-oxidation effects and an inhibition of inflammation factors releasing.

Amrinone ; therapeutic use ; Animals ; Interleukin-1beta ; blood ; Interleukin-8 ; blood ; Lung ; blood supply ; drug effects ; Male ; Malondialdehyde ; analysis ; Phosphodiesterase Inhibitors ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; metabolism ; pathology ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo study the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in the course of asthma airway remodeling, to explore whether IL-1beta participates in asthma airway remodeling mediated by JNK signal transduction pathway.

METHODSTotally 72 male Sprague-Dawlay rats (6 - 8 weeks old, weighing about 120 g) were randomly divided into control groups (36 rats) and asthma groups (36 rats). The rats were sensitized for inducing asthma by intraperitoneal injection of ovalbumin and AL(OH)3 and were repeatedly exposed to aerosolized ovalbumin for 4, 8, 12 weeks (A4, A8, or A12 group), each had 12 rats, and correspondingly control rats were intraperitoneally injected with 0.9% NaCl, then were repeatedly exposed to 0.9% NaCl for 4, 8, 12 weeks (C4, C8, or C12 group), each had 12 rats. The ultrastructural changes of pulmonary tissues were observed by transmission electron microscope (TEM). The total bronchial wall thickness (Wat) and the airway smooth muscle thickness (Wam) were measured by an image analysis system. The concentrations of IL-1beta in serum and bronchoalveolar lavage fluid (BALF) were tested by a "sandwich" ELISA. The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique. Lung tissue extracts were analyzed for phosphorylation of JNK by Western blotting. Linear correlation analysis showed the correlation between Wat and P-JNK protein, Wam and P-JNK protein, levels of IL-1beta in serum and P-JNK protein, levels of IL-1beta in BALF and P-JNK protein.

RESULTSIn asthma groups, TEM showed alveolar septal proliferation and alveolus type II epithelial cells swelling. Wat and Wam in all asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), and compared with group A4 and group A8, Wat and Wam of group A12 significantly increased (P < 0.01). The concentrations of IL-1beta in serum and BALF of asthma groups were all significantly higher than those of the corresponding control groups (P < 0.01, respectively), and compared with group A4 and group A8, the concentrations of IL-1beta in BALF of group A12 significantly increased (P < 0.01 or P < 0.05), but the levels of IL-1beta in serum were not significantly different among them (P > 0.05). Mean absorbance values (by immunohistochemistry) of P-JNK and P-c-Jun in asthma groups were significantly higher than those in corresponding control groups (P < 0.01, respectively), and compared with group A4 and group A8, those of group A12 significantly increased (P < 0.01 or P < 0.05). The absorbance (by Western Blot) of P-JNK in A4, A8, A12 group was significantly higher than that in C4, C8, C12 groups (P < 0.01, respectively), and compared with group A4, that of P-JNK of A12 significantly increased (P < 0.01), and compared with group A8, there was no significant difference (P > 0.05). Strong positive correlations were found between Wat or Wam and P-JNK (r = 0.823 and r = 0.818, P < 0.01, respectively, n = 68) and between P-JNK and concentration of IL-1beta in serum or BALF (r = 0.717 and r = 0.803, P < 0.01, respectively, n = 68).

CONCLUSIONSThe expression of P-JNK and its downstream P-c-Jun in rats of asthma airway remodeling is increased, which implicates that JNK signal transduction pathway plays an important role in the course of asthma airway remodeling. IL-1beta participates in asthma airway remodeling possibly partly through activating JNK signal transduction pathway.

Airway Remodeling ; Animals ; Asthma ; metabolism ; physiopathology ; Interleukin-1beta ; blood ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction