OBJECTIVETo identify the differential expressions of serum cytokines between prostate cancer (PCa) and benign prostatic hyperplasia (BPH), and provide proteomic evidence for the early diagnosis of PCa.

METHODSWe used human cytokine array to determine the profiles of the serum cytokines obtained from 6 PCa and 6 BPH patients with the PSA level within the grey scale of 4 - 10 ng/ml.

RESULTSWe identified 19 differentially expressed cytokines in the PCa patients, 16 obviously up-regulated, including IL-3, IL-6 and IL-16, and 3 markedly down-regulated, which were Fas/TNFRSF6, TRALR-3 and IGFBP-6. Most of them were involved in such cellular bioprocesses as transcription, proliferation, signal transduction, and apoptosis.

CONCLUSIONThe cytokine antibody assay permits simultaneous measurement of multiple markers in a small volume of serum, and can identify a panel of key cytokines related to the malignant biological behavior of cancer cells. And it helps to find the biomarkers for the early diagnosis, efficacy assessment and prognosis of prostate cancer.

Aged ; Humans ; Interleukin-16 ; blood ; Interleukin-3 ; blood ; Interleukin-6 ; blood ; Male ; Middle Aged ; Prostatic Hyperplasia ; blood ; genetics ; metabolism ; Prostatic Neoplasms ; blood ; genetics ; metabolism ; Proteomics

A main symptom of equine metabolic syndrome (EMS) in ponies is pathological obesity characterized by abnormal accumulation of fat deposits and inflammation. In this study, we analyzed the expression of two pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), in subcutaneous adipose tissue and the correlation with serum concentrations in peripheral blood of Welsh ponies. Based on clinical examination findings, the animals were divided into two groups: ponies affected with EMS (n = 8) and obese ponies (n = 8). The adipose tissue was examined using immunohistochemical analysis while concentrations IL-6 and TNF-alpha were measured using enzyme-linked immunosorbent assays (ELISAs). Additionally, histological characterization of the adipose tissue was performed. The results obtained showed that IL-6 expression in adipose tissue biopsies derived from animals with EMS was enhanced while TNF-alpha levels of both groups were comparable. Compared to the obese ponies, EMS animals also had significantly elevated levels of serum IL-6 and TNF-alpha. Histological analysis revealed macrophage infiltration and fibrosis in adipose tissue preparations from the EMS group. These data suggest that IL-6 may play a key role in the course of EMS in Welsh ponies. Our findings also demonstrated that analysis of pro-inflammatory cytokines levels in serum may serve as an additional tool for diagnosing EMS.
Adipose Tissue/*metabolism ; Animals ; Female ; Horse Diseases/blood/*metabolism ; Horses ; Interleukin-6/blood/genetics/*metabolism ; Male ; Metabolic Syndrome X/metabolism/*veterinary ; Tumor Necrosis Factor-alpha/blood/genetics/*metabolism

OBJECTIVETo evaluate the mechanism and influence of thalidomide on interleukin-6 (IL-6), IL-6 receptor (IL-6R) and its transmitting chain in multiple myeloma patients.

METHODSSerum level of IL-6, expression of IL-6R on myeloma cells and IL-6R beta mRNA in multiple myeloma patients were measured by enzyme linked immunosorbent assay (Elisa), flow cytometry and reverse transcription polymerase chain reaction (RT-PCR).

RESULTSSerum level of IL-6 in multiple myeloma patients was 564.8 +/- 319.4 ng/L, with a positive rate on the myeloma cells of 33.6% before oral 200 mg/d thalidomide. They were 560.3 +/- 414.8 ng/L and 31.8% on D14 after oral 200 mg/d thalidomide, which were not significantly different as compared with those before (P > 0.05). On D14, 28, 42, 56 and 84 after oral 400 mg/d thalidomide, the serum level of IL-6 in multiple myeloma patients were 516.7 +/- 131.9 ng/L, 426.7 +/- 180.4 ng/L, 387.9 +/- 187.4 ng/L, 350.1 +/- 85.5 ng/L and 212.3 +/- 92.5 mg/L, with positive rates on the myeloma cells of 28.5%, 24.3%, 21.3%, 12.6% and 10.1%, which were all lower than those before oral 200 mg/d thalidomide (P < 0.05 or P < 0.01). Ratios before and on D14 after oral 200 mg/d thalidomide were 7.8 and 6.9, with no statistical significance (P > 0.05). Ratios on D14, 28 after oral 400 mg/d thalidomide were 5.3 and 2.7, which were lower than those before oral 200 mg/d thalidomide (P < 0.01).

CONCLUSIONReduction of serum level of IL-6 in multiple myeloma patients and decrease in IL-6R expression on the myeloma cells and IL-6R beta mRNA occur on D14 after oral 400 mg/d thalidomide. These changes become more obvious with time. The antitumor mechanism of thalidomide may be related to reduction of IL-6 serum level in multiple myeloma patients and decrease in IL-6R expression on the myeloma cells and IL-6R beta mRNA.

Aged ; Angiogenesis Inhibitors ; pharmacokinetics ; pharmacology ; Female ; Humans ; Interleukin-6 ; blood ; genetics ; Male ; Middle Aged ; Multiple Myeloma ; blood ; metabolism ; RNA, Messenger ; drug effects ; metabolism ; Receptors, Interleukin-6 ; metabolism ; Thalidomide ; pharmacokinetics ; pharmacology

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

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

OBJECTIVETo investigate effect of Chaiqin Chengqi Decoction (, CQCQD) on changes of neuronal acetylcholine receptor alpha 7 (nAChRα7) of peritoneal macrophages in acute pancreatitis (AP).

METHODSEighteen Kunming mice were equally randomized into the control group, AP group and CQCQD treatment group. AP was induced by two intraperitoneal injections of 4 g/kg L-arginine at 1 h apart, while control mice received saline injections. At 72 h after the first injection of L-arginine, mice in the treatment group were intragastrically administered 0.1 mL/10 g CQCQD every 2 h for 3 times, whilst mice in the other two groups received the same amount of saline feeding. Mice were sacrificed by cervical dislocation 2 h after the last feeding of either CQCQD or saline. Peritoneal macrophages were collected for determination of nAChRα7 mRNA and protein expression. Serum was collected for detection of interleukin-6 (IL-6), IL-10 and acetylcholine (ACh) levels, and pancreas was for histopathology analysis.

RESULTSThe CQCQD treatment significantly ameliorated the severity of AP as evidenced by reducing the pancreatic histopathology score (4.5±0.5 vs. 6.2±1.7, P<0.05) and the serum IL-6 levels (1228.3±419.2 pg/mL vs. 1589.6±337.3 pg/mL, P<0.05). The mRNA and protein expression of nAChRα7 of the peritoneal macrophages in the AP group were similar to the control group (P>0.05), but were significantly up-regulated after the CQCQD treatment (P<0.05). The serum ACh levels in the AP group were significantly lower than those in the control group (3.1±0.6 μg/mL vs 4.8±0.7 μg/mL P<0.05), but were significantly increased after the CQCQD treatment (5.6±1.5 μg/mL vs 3.1±0.6 μg/mL, P<0.05).

CONCLUSIONCQCQD is protective against L-arginine-induced AP through mechanisms involving nAChRα7 of peritoneal macrophages.

Acetylcholine ; pharmacology ; Acute Disease ; Animals ; Blotting, Western ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Macrophages, Peritoneal ; drug effects ; metabolism ; pathology ; Mice ; Neurons ; drug effects ; metabolism ; Pancreas ; drug effects ; pathology ; Pancreatitis ; blood ; drug therapy ; pathology ; RNA, Messenger ; genetics ; metabolism ; alpha7 Nicotinic Acetylcholine Receptor ; genetics ; metabolism

This study is to investigate the pharmacological effect and mechanism of action of hydroxysafflor yellow A (HSYA) on acute lung injury (ALI). The rat ALI was induced by oleic acid and lipopolysaccharide (LPS) injection. The incidence of acidosis, PaO2 (arterial blood oxygen pressure), W/D (wet weight/dry weight) and lung index (LI) were measured. Electron microscope and optical microscope were applied to observe lung morphological changes in rat. RT-PCR was used to determine TNF-alpha and ICAM-1 mRNA level. Inhibition effect of HSYA on plasma inflammatory cytokine expression was measured by ELISA. HSYA could alleviate pulmonary edema, reduce acidosis, keep PaO2 from descending, inhibit inflammatory cell infiltration, inhibit rat lung TNF-alpha and ICAM-1 mRNA expression and plasma IL-6 and IL-1beta level elevation. HSYA is an effective ingredient to remit ALI induced by oleic acid and LPS in rat.
Acute Lung Injury ; chemically induced ; metabolism ; pathology ; Animals ; Carthamus tinctorius ; chemistry ; Chalcone ; analogs & derivatives ; isolation & purification ; pharmacology ; Flowers ; chemistry ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Lipopolysaccharides ; Lung ; metabolism ; pathology ; ultrastructure ; Male ; Oleic Acid ; Plants, Medicinal ; chemistry ; Quinones ; isolation & purification ; pharmacology ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

This study was purposed to investigate the effect of multiple myeloma patients' sera on hepcidin mRNA expression of Hep-3b hepatoma cell line and effect of human interleukin-6 (IL-6) antibody or recombinant human erythropoietin (rhEPO) on hepcidin mRNA expression. The clinical information and serum of multiple myeloma patients were collected. Their sera of a final concentration of 10% were added into Hep-3b cell medium. The mRNA from Hep-3b cells was extracted, and hepcidin mRNA expression was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). A final concentration of 10 ng/ml human IL-6 antibody and 2 U/ml rhEPO were added into the medium respectively. The results showed that the sera of untreated multiple myeloma patients elevated hepcidin mRNA expression of Hep-3b cells, compared with healthy controls and iron deficiency anemia patients. This effect was fully neutralized by human IL-6 antibody or rhEPO. The hemoglobin (Hb) level was stable during the follow up of regularly treated multiple myeloma patients and the effect of MM patient serum on Hep-3b cell hepcidin mRNA expression was reduced. It is concluded that the hepcidin mRNA expression of Hep-3b cell can be increased by untreated multiple myeloma patient serum. This promotive effect can be antagonised by IL-6, which suggests that IL-6 may be possible to elevate expression level of hepcidin in Hep-3b cells and results in anemia of chronic disease (ACD). The above mentioned promotive effects also can be suppressed by rhEPO, which indicates that the rhEPO may possess curative effect for ACD disease. During short-term follow-up of treated patients with multiple myeloma the Hb level is stable, the influence of patients serum on hepcidin mRNA of Hep-3b cells decreases, which shows the stabilization of disease and amelioration of ACD patient status.
Adult ; Aged ; Antibodies, Monoclonal ; pharmacology ; Antimicrobial Cationic Peptides ; genetics ; Cell Line, Tumor ; Erythropoietin ; blood ; pharmacology ; Female ; Hepcidins ; Humans ; Interleukin-6 ; immunology ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; metabolism ; RNA, Messenger ; genetics

BACKGROUNDTumor necrosis factor (TNF)-α plays an important role in mediating inflammatory state in obesity and related disorders. Lipopolysaccharides (LPS)-induced TNF-α factor (LITAF) is recently verified as a regulator of TNF-α and other inflammatory cytokines, and maybe act as a transcriptional factor. The aim of this study was to confirm the association between LITAF and obesity and insulin resistance.

METHODSForty-seven subjects with a wide range of body mass index (BMI) were included. Subjects were divided into three groups according to the criteria of normal weight, overweight and obese. Anthropometrics and metabolic profile were tested for all the subjects. Peripheral monocytes were isolated and purified. LITAF transcription was detected by real time PCR, and the protein expression in whole cell and nucleus extracts was detected by Western blotting analysis; transcriptional activity of LITAF was detected by ELISA like assay using a probe containing the DNA binding sequence of LITAF. Plasma TNF-α and interleukin (IL)-6 concentrations were determined with ELISA kit.

RESULTSThe LITAF mRNA and protein expression in whole cell were higher in overweight (P < 0.05) and obese group (P < 0.05) compared with that in normal weight group. The LITAF protein expression in the nucleus and transcriptional activity could not be detected. LITAF protein expression was positively correlated with BMI (r = 0.541, P < 0.001), waist circumference (r = 0.391, P = 0.007), the homeostasis model assessment for insulin resistance (r = 0.372, P = 0.011) and fasting insulin levels (r = 0.359, P = 0.013). As a regulator of inflammatory cytokines, LITAF protein expression was positively correlated with plasma TNF-α (r = 0.621, P = 0.002) and IL-6 (r = 0.407, P = 0.039) concentration. Multiple variant regression analysis indicated that BMI (P = 0.002) and waist circumference (P = 0.017) were independent predictors of LITAF protein expression.

CONCLUSIONSLITAF is associated with obesity and insulin resistance, as well as inflammatory cytokine secretion. The results indicate LITAF to be a new mediator between inflammation and the obesity related disorders.

Adult ; Anthropometry ; Blotting, Western ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Insulin Resistance ; genetics ; physiology ; Interleukin-6 ; blood ; Leukocytes, Mononuclear ; metabolism ; Male ; Nuclear Proteins ; genetics ; metabolism ; Obesity ; blood ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; blood