OBJECTIVETo investigate the effect of FK506 on cytokine secretions in whole blood from healthy individuals.

METHODSBlood samples collected from healthy volunteers were co-cultured with different concentrations of FK506 and stimulated with PMA and IONO. The concentrations of 8 cytokines including IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha, GM-CSF and G-CSF were detected by Bio-Plex suspension system.

RESULTSCompared with the control group, high-concentration FK506 (20 ng/ml) significantly inhibited the secretions of IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha, GM-CSF and G-CSF. At a moderate concentration (5 ng/ml), FK506 inhibited the secretion of GM-CSF significantly.

CONCLUSIONFK506 effectively inhibits the secretion of proinflammatory cytokines including IL-6, IFN-gamma and TNF-alpha and also the secretion of IL-2, IL-12, IL-17, GM-CSF and G-CSF. FK506 might play the role of immunosuppression by inhibiting the production of these cytokines by the immune cells. Monitoring the levels of these cytokines might be a potential method for evaluating the adequacy of FK506 doses administered.

Adult ; Cytokines ; blood ; secretion ; Down-Regulation ; drug effects ; Female ; Humans ; Immunosuppressive Agents ; pharmacology ; Interferon-gamma ; blood ; secretion ; Interleukin-6 ; blood ; secretion ; Male ; Tacrolimus ; pharmacology ; Tumor Necrosis Factor-alpha ; blood ; secretion ; Young Adult

Sparganosis is a tissue invading helminthiasis infecting intermediate hosts, including humans. Strong immune responses are expected to occur in early phases of infection. Thus, we investigated cytokine expressions in splenic dendritic cells and in sera after experimental infection of mice. In splenic dendritic cells, TNF-alpha and IL-1beta expression peaked at week 1 and week 3 post-infection (PI), respectively, and also early phase (week 2 PI) depressed cytokine expression was noticed. Serum IL-1beta concentration increased significantly at week 2 PI and peaked at week 6 PI, and that of TNF-alpha peaked at week 6 PI. These results showed that pro-inflammatory cytokines, TNF-alpha and IL-1beta, are chronologically regulated in mouse sparganosis.
Animals ; Dendritic Cells/*immunology ; Disease Models, Animal ; Interleukin-1beta/*blood/*secretion ; Mice ; Mice, Inbred BALB C ; Rodent Diseases/immunology ; Serum/chemistry ; Sparganosis/*immunology ; Spleen/*immunology ; Tumor Necrosis Factor-alpha/*blood/*secretion

OBJECTIVETo confirm the efficacy and safety of Jitongning Capsule in the treatment of ankylosing spondylitis (AS).

METHODSA total of 120 AS patients with early-intermediate were randomly and equally assigned to Jitongning Capsule group and sulfasalazine group. Jitongning Capsule was orally taken 4.5 g per day and sulfasalazine was orally taken 2 g daily for 12 months. The primary endpoint was the proportion of patients achieving the Assessment in Ankylosing Spondylitis 20 (ASAS 20), secondary end points included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), patient's global assessment by VAS rating, spinal pain, general pain and night pain, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMC) of AS patients were measured.

RESULTSA total of 111 patients completed the study. There were 58 patients in Jitongning group and 53 patients in sulfasalazine group. Both drugs showed mild and occasional side effects. After treated by Jitongning Capsule and sulfasalazine, the proportion of ASAS20 responders at 12 month was 72.41% (42/58) and 67.92% (36/53) respectively. Both Jitongning Capsule and sulfasalazine treatment induced significant decrease in the proportion of CD4(+)T cell and CD8(+)T cell expressing TNF-&alpha; and IFN-γ at 12-month of treatment compared with baseline values (P<0.05).

CONCLUSIONJitongning Capsule are effective in a setting close to real-life medical care with a sustained improvement in signs and symptoms of AS, and reduce cytokine levels in PBMC. It showed comparable effects to sulfasalazine.

Adult ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; CD4-Positive T-Lymphocytes ; drug effects ; secretion ; CD8-Positive T-Lymphocytes ; drug effects ; secretion ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Endpoint Determination ; Female ; Flow Cytometry ; Humans ; Interferon-gamma ; secretion ; Interleukin-4 ; secretion ; Male ; Middle Aged ; Spondylitis, Ankylosing ; blood ; drug therapy ; immunology ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; secretion ; Young Adult

This investigation was made in regard to the changes of plasma Leptin, Tumor Necrosis Factor-alpha (TNF-alpha) and Neuropeptide Y (NPY) levels and their association with insulin resistance and beta-cell secretion function in normal glucose tolerant first-degree relatives of familial type 2 diabetic pedigrees in Chengdu area. Levels of Leptin, TNF-alpha, NPY and lipids (TG, TC, HDL-C) were determined in 86 type 2 diabetic mellitus (DM) patients, 73 normal glucose tolerant (NGT) first-degree relatives in familial type 2 diabetic pedigrees and 65 normal controls (NC) from non-diabetic families. All of the subjects underwent 75 g oral glucose tolerance test (OGTT). Plasma glucose, immunoreactive insulin (IRI) and true insulin (TI) levels were also determined. Fasting glucose and TI levels were used to calculate homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-beta cell indexes. After being adjusted for age and body mass index (BMI), the levels of Leptin in DM and NGT first-degree relatives were all significantly higher than that in normal controls (P < 0.05). Type 2 diabetic patients showed significantly elevated TNF-alpha levels than did the normal controls (P < 0.05). Furthermore, diabetic subjects showed significantly higher HOMA-IR and lower HOMA-B levels, compared with those in NGT and NC groups (P < 0.05). No statistically significant difference was found in regard to NPY among three groups. NGT first-degree relatives showed significantly higher levels of TG, fasting IRI, OGTT-2h IRI and HOMA-IR than did the normal controls (P < 0.05). Leptin was positively correlated with age, BMI, waist, A1c, fasting and OGTT-2h glucose, OGTT-2h TI and TNF-alpha in all subjects, and was negatively correlated with HOMA-B in females. Leptin levels were significantly elevated in NGT first-degree relatives, which implied that genetic defects of Leptin may play a role in the development of familial type 2 diabetic pedigrees.
Adult ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Female ; Glucose Tolerance Test ; Humans ; Insulin ; secretion ; Insulin Resistance ; Leptin ; blood ; Male ; Middle Aged ; Neuropeptide Y ; blood ; Pedigree ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo observe the effect of formula of removing both phlegm and blood stasis (TYTZ) in inhibiting the inflammatory reaction in Chinese mini-swine with coronary atherosclerosis.

METHODTotally 36 Chinese mini-swine were randomly divided to six groups: the normal control group, the model group, the Shujiangzhi group and TYTZ groups with does of 2.0, 1.0 and 0.5 g x kg(-1), and six each in every group. Except for the normal control group, all of other groups were fed with high-fat diet for 2 weeks. Interventional balloons are adopted to injure their left anterior descending artery endothelium. After the operation, they were fed with high-fat diet for 8 weeks to prepare the coronary atherosclerosis model. In the 8th week after the operation and administration, the intravascular ultrasound was adopted to observe the coronary artery plaque burden of each group and the pathological morphology of coronary artery. Such inflammatory factors as high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were detected by ELISA. The expression of NF-kappaB p65 nuclear translocation was observed by the immunohistochemical method.

RESULTCompared with the normal control group, the model group showed significant increase in the coronary artery plaque burden at the end of the experiment (P < 0.01), notably abnormal structural changes in atherosclerotic vascular tissues, luminal stenosis, a large number of foam cells and inflammatory cell infiltration, remarkable growth of hs-CRP, TNF-alpha and IL-6 levels (P < 0.01). The immunohistochemical staining also showed the significant increase in the NF-kappaB p65 nuclear translocation of coronary artery of Chinese mini-swine in the model group. Compared with the model group, TYTZ could significantly attenuate atherosclerotic plaque burden (P < 0.01), inhibit the coronary luminal stenosis, reduce inflammatory cell infiltration, decrease such inflammatory cell factors as hs-CRP, TNF-alpha and IL-6 in serum, and inhibit the NF-kappaB p65 nuclear translocation of coronary artery (P < 0.05 or P < 0.01).

CONCLUSIONTYTZ can reduce the downstream inflammatory reaction by controlling NF-kappaB p65 nuclear translocation, so as to inhibit the occurrence and development of coronary atherosclerotic plaque in Chinese mini-swine.

Animals ; C-Reactive Protein ; metabolism ; Coronary Artery Disease ; blood ; complications ; drug therapy ; pathology ; Female ; Inflammation ; complications ; Interleukin-6 ; blood ; Male ; Medicine, Chinese Traditional ; methods ; Mucous Membrane ; drug effects ; secretion ; Swine ; Swine, Miniature ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the effect of dihydro-qinghaosu (DQHS) on auto-antibody production, TNF alpha secretion and pathologic change of lupus nephritis in BXSB mice and the possible mechanism of DQHS in treating systemic lupus erythematosus (SLE).

METHODSAnti ds-DNA antibody and TNF alpha in serum of the BXSB mice were detected by enzyme linked immunosorbent assay (ELISA). Renal tissue was stained by HE and Masson.

RESULTSIn the height and moderate dose DQHS groups, as compared with the model group, levels of anti-ds-DNA antibody and serum TNF alpha were significantly lower (P < 0.05); and renal pathological change was milder.

CONCLUSIONDQHS could inhibit the production of anti-ds-DNA antibody and secretion of TNF alpha and improve the pathologic lesion of lupus nephritis in BXSB mice.

Animals ; Antibodies, Antinuclear ; blood ; Artemisinins ; pharmacology ; Immunosuppressive Agents ; pharmacology ; Lupus Erythematosus, Systemic ; immunology ; pathology ; Lupus Nephritis ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Random Allocation ; Sesquiterpenes ; pharmacology ; Tumor Necrosis Factor-alpha ; secretion

OBJECTIVETo investigate the relationship between four cytokines in serum and prostatic fluid and chronic abacterial prostatitis (CAP).

METHODSThe levels of interleukin-2 (IL-2), IL-4, IL-8, tumor necrosis factor-alpha (TNF-alpha) were detected in 86 patients with CAP [CAP I (n = 60), WBC > or = 10/HP; CAP II (n = 26, WBC < 10/HP)], and 20 healthy males as control by ELISA.

RESULTSIL-2, IL-8 and TNF-alpha in serum and prostatic fluid, and IL-4 in serum in patients with CAP I were markedly higher than those in the control, respectively (P < 0.05 or P < 0.01). No significant difference was observed in IL-4 level in prostatic fluid among CAP I, CAP II and control groups respectively (P > 0.05), and in IL-2, IL4, TNF-alpha in serum and prostatic fluid between CAP II group and the control (P > 0.05). IL-8 was correlated with WBC number in prostatic fluid (r = 0.62, P < 0.05).

CONCLUSIONIL-2, IL-8, TNF-alpha may play roles in the process of pathogenesis of CAP, and they have applicable value in the diagnosis and typing of CAP.

Adult ; Bodily Secretions ; chemistry ; Chronic Disease ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-8 ; metabolism ; Male ; Middle Aged ; Prostate ; secretion ; Prostatitis ; blood ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo isolate and purify a new type of lipopolysaccharide binding protein (LBP) from burn rabbit serum, and to investigate its biological functions.

METHODSRabbits subjected to burn injury and endotoxemia were employed. The serum from the rabbits was purified by two-steps of ion-exchange chromatography (Bio-Rex 70 Resin, Mono-Q) and gel chromatography. Furthermore, the serum was identified by flow cytometry analysis, agglomeration test with sheep erythrocyte, and amino end amino acid residue sequencing. The obtained protein was applied to cultured human monocytes (U937), and the cytokine secretion such as TNFalpha from the U937 was observed.

RESULTSThe molecular weight of the harvested protein was 48 kDa, and the 10 amino acid sequence at N end was arranged as GSQGTFTSEE, which was different to the amino acid sequence in NCBI protein bank and was so named P48. P48 possessed similar function to that of LBP and could promote the binding of LPS in a very low concentration with peripheral blood monocytes (PBMC), and also promote the TNFalpha secretion from U937.

CONCLUSIONP48, a new type of LBP, could be isolated and purified from the burn rabbit serum. P48 possessed similar biological activities to that of LBP and could promote the process of inflammatory reaction.

Acute-Phase Proteins ; Amino Acid Sequence ; Animals ; Binding, Competitive ; drug effects ; Blood Proteins ; chemistry ; isolation & purification ; pharmacology ; Burns ; blood ; Carrier Proteins ; chemistry ; isolation & purification ; pharmacology ; Chromatography, Gel ; Chromatography, Ion Exchange ; Female ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear ; cytology ; drug effects ; metabolism ; Lipopolysaccharides ; metabolism ; Male ; Membrane Glycoproteins ; Rabbits ; Sequence Analysis, Protein ; Tumor Necrosis Factor-alpha ; secretion ; U937 Cells

This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage with water, Met group with metformin hydrochloride at a dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT) were determined. Beta cell function was assessed by hyperglycemic clamp. Pancreatic biochemical indicators were tested. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR and immunostaining. Met significantly improved glucose intolerance and insulin resistance in KKAy mice. Fasting plasma glucose and insulin levels were also decreased. In addition, Met markedly increased glucose infusion rate (GIR) and elevated the Ist phase and maximum insulin secretion during clamp. It showed that Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase activity in pancreas. Islets periphery was improved, and down-regulation of glucagon and up-regulated insulin protein expressions were found after Met treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF-κB, JNK, IL-6 and TNF-&alpha; were down-regulated, p-NF-κB p65 protein levels also down-regulated by Met. And mRNA expressions of ion homeostasis involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the hyperglycemic clamp. These results indicated that chronic administration of Met regulated pancreatic inflammation generation, ion and hormone homeostasis and improved β cell function of diabetic KKAy mice.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; drug therapy ; Down-Regulation ; Female ; Glucose Tolerance Test ; Homeostasis ; Inflammation ; drug therapy ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Interleukin-6 ; metabolism ; Metformin ; pharmacology ; Mice ; NF-kappa B ; metabolism ; Pancreas ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism