OBJECTIVE: To assess the impact of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis patients. METHODS: The study included patients over 18 years old who had been treated by biological agents for at least 24 weeks for moderate to severe plaque psoriasis from Novermber 2015 to January 2024. According to the biological agents the patients used, they were divided into three groups: interleukin-17 (IL-17) inhibitor group, IL-23 and IL-12/23 inhibitor group and tumor necrosis factor-α (TNF-α) inhibitor group. The metabolic biochemical parameters of each group were evaluated and compared before and after the administration of the biologic therapies. RESULTS: A total of 174 patients with moderate to severe plaque psoriasis were included in the long-term treatment with biologics, including 127 males (73.00%), 47 females (27.00%), with a median age of 38.00 (31.50, 49.00) years and a median duration of psoriasis of 12.00 (10.00, 20.00) years. The median duration of biologic treatment was 61.00 (49.00, 96.25) weeks, ranging from 26 to 301 weeks. There were 101 patients in the IL-17 inhibitor group, 38 patients in the IL-23 and IL-12/23 inhibitor group, and 35 patients in the TNF-α inhibitor group. After long-term treatment with IL-17 inhibitors, no statistically significant changes were observed in body weight, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose (GLU), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with baseline measurements (P>0.05). However, low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced [(2.90±0.75) mmol/L vs. (3.05±0.79) mmol/L, t=－2.100, P=0.038], while uric acid (UA) levels showed a significant increase [(401.13±99.13) μmol/L vs. (364.94±91.11) μmol/L, t=5.215, P < 0.001]. The group with normal UA levels before treatment showed a significant increase after long-term application of biological agents compared with before treatment [(370.69± 89.59) μmol/L vs. (324.66±64.50) μmol/L, t=5.856, P < 0.001]. Following long-term application of IL-23 and IL-12/23 inhibitors, no statistically significant differences were observed in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C and UA levels when compared with baseline measurements (P> 0.05). However, LDL-C levels exhibited a significant reduction from baseline [(2.85±0.74) mmol/L vs. (3.12±0.68) mmol/L, t=－2.082, P=0.045]. After long-term treatment with TNF-α inhibitor, there were no significant differences in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C, LDL-C and UA compared with baseline measurements (P>0.05). CONCLUSION Long-term application of IL-17 inhibitors in moderate to severe plaque psoriasis patients may result in elevated uric acid levels, particularly in patients with normal uric acid levels before treatment. The long-term use of IL-17 inhibitors, IL-23 inhibitors or IL-12/23 inhibitors might reduce LDL-C levels.
Humans ; Psoriasis/blood* ; Male ; Female ; Adult ; Middle Aged ; Interleukin-17/antagonists & inhibitors* ; Interleukin-23/antagonists & inhibitors* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Interleukin-12/antagonists & inhibitors* ; Biological Therapy ; Biological Products/therapeutic use* ; Triglycerides/blood* ; Cholesterol, LDL/blood* ; Cholesterol, HDL/blood*

OBJECTIVETo investigate the effects of antihistamine treatment on immune function in rats with experimental hepatitis.

METHODSThirty Wistar rats were randomly allocated into three groups:experimental hepatitis group (EH group), antihistamine treatment group (AH group) and normal control group (NC group). Rats in the EH group received the subcutaneous injection of 40% carbon tetrachloride oil solution and were fed on diet with low-protein, low-choline, high-fat and high-alcohol,while rats in the AH group received antihistamine treatment(ketotifen + vitamin C) additionally.They were sacrificed after 4 weeks, and the levels of serum alanine aminotransferase(ALT), total bilirubin (TBil), histamine(HA), IFNgamma, IL-12, IL-4 and IL-10 were determined. The levels of IL-12 mRNA and IFN-gamma mRNA in liver tissue were determined via real-time reverse transcriptional polymerase chain reaction(RT-PCR).

RESULTS(1) Compared to the NC group, in the EH group, the levels of ALT, TBil, and circulating and intrahepatic HA were significantly increased(P less than 0.05); intrahepatic HA were significantly decreased(P less than 0.05) after antihistamine treatment. (2) Compared to the NC group, in the EH group, the levels of IL-4, IL-10 were significantly increased((0.504+/-0.202)ng/ml and (29.025+/-1.478) pg/ml vs (0.811+/-0.244)ng/ml and (33.72+/-4.293)pg/ml respectively, P less than 0.05), and the levels of IL-12 were decreased ((6.515+/-2.893)pg/ml vs (3.519+/-1.113)pg/ml, P less than 0.05); and after antihistamine treatment the levels of IL-4 and IL-10 were significantly decreased (were (0.423+/-0.168)ng/ml and (30.412+/-3.275)pg/ml, P less than 0.05), the levels of IL-12 were significantly increased (P less than 0.05), but the level of IFNgamma had no significance (P more than 0.05). The levels of intrahepatic IL-12 mRNA and IFNgamma mRNA had similar results.

CONCLUSIONAntihistamine treatment may improve liver function and correct Th1/Th2 unbalance.

Animals ; Ascorbic Acid ; pharmacology ; Disease Models, Animal ; Hepatitis ; immunology ; metabolism ; therapy ; Histamine Antagonists ; pharmacology ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; metabolism ; Ketotifen ; pharmacology ; Liver ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar ; Th1-Th2 Balance ; Tumor Necrosis Factor-alpha ; metabolism

Taxol has been used effectively in cancer therapies. Our previous study demonstrated that taxol induced altered maturation and improved viability of dendritic cells (DCs). However, the effects of taxol on DC viability have not been fully elucidated. In the present study, flow cytometric analyses revealed that taxol treatment significantly increased the number of viable DCs and the expression levels of a representative anti-apoptotic protein Bcl-xL. Furthermore, mobilization of the p65 subunit of nuclear factor-kappaB (NF-kappaB) from the cytosol to the nucleus in DCs was observed by confocal microscopy. An inhibition assay using N-p-tosyl-L-phenylalanine chloromethyl ketone confirmed that NF-kappaB was intimately involved in the effects of taxol on DC viability. In addition, we investigated the mechanisms of taxol enhancement of DC viability. Since taxol is a popular anticancer agent used in clinic, this study may provide a rationale for the use of taxol in DC immunotherapy to treat cancer patients. Taken together, these results confirm that taxol increases DC viability, and this information may provide new insights for new clinical applications of both taxol and DCs.
Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Blotting, Western ; Cell Survival/drug effects/physiology ; Dendritic Cells/cytology/*drug effects/physiology ; Female ; Flow Cytometry ; Interleukin-12/physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microscopy, Confocal ; Paclitaxel/*pharmacology ; Tosylphenylalanyl Chloromethyl Ketone/pharmacology ; Transcription Factor RelA/antagonists & inhibitors/*physiology ; Tumor Necrosis Factor-alpha/physiology ; bcl-X Protein/*physiology

OBJECTIVE: To explore the effect of suppressive oligodeoxynucleotides (Sup ODN) on the Th1 differentiation of CD4(+)T splenetic lymphocytes in mice. METHODS: The splenetic lymphocytes of BALB/c mice were separated, and then CD4(+) cells were purified with immune magnetic CD4(+) microbeads (positive selection). The purification was examined by fluorescence-activated cell sorter. CD4(+) cells, anti-CD3epsilon, anti-CD28, IL-12 and Sup ODN or control oligodeoxynucleotides (Con ODN) were co-incubated for 72 h. IFN-gamma and IL-4 in the supernatant were detected using enzyme-linked immunosorbent assay. The expression of T-bet mRNA in CD4(+) cells was tested by reverse transcription polymerase chain reaction. RESULTS: Sup ODN could significantly inhibit the release of INF-gamma and increase IL-4 production respectively (P<0.01). T-bet mRNA of CD4(+) lymphocytes was remarkably inhibited by Sup ODN as well (P<0.01). CONCLUSION In the presence of pro-Th1-cytokines, Sup ODN may affect the differentiation of CD4(+) T lymphocytes in vitro. Sup ODN can promote CD4(+) T cells to differentiate into Th2, and suppress them into Th1.
Animals ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; cytology ; immunology ; Cell Differentiation ; drug effects ; Female ; Interferon-gamma ; antagonists & inhibitors ; physiology ; Interleukin-12 ; antagonists & inhibitors ; physiology ; Mice ; Mice, Inbred BALB C ; Oligodeoxyribonucleotides ; pharmacology ; T-Lymphocyte Subsets ; Th1 Cells ; cytology ; immunology

OBJECTIVETo investigate therapeutic potential of TRAIL in hepatocellular carcinoma (HCC) and the mechanism of sTRAIL resistance and to reverse the resistance to sTRAIL-inducing apoptosis.

METHODSThe expression profiles of TRAILR were determined 60 HCC samples, in 20 normal liver tissues and 2 HCC cell lines HepG2 and SMMC-7721 by in situ hybridization. Cellular effects of sTRAIL in promoting apoptosis on HCC cell lines HepG2 and SMMC-7721 were analyzed after exposure to recombinant protein and after transfection with a cDNA expression construct. In vivo effects of sTRAIL on tumor growth were investigated using a nude mice HCC model of hepG2. Furthermore, the expression of survivin in HCC was detected, and treatment with antisence oligonucleotide was accepted. Finally, therapeutic effect on HCC by combining sTRAIL and interleukin-12 (IL-12) was detected.

RESULTSBoth DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. Recombinant sTRAIL alone was found to have a slight activity as it killed a maximum of 15% of HCC cells within 24 h while killing over 70% of Jurkat cells. In vivo administration of the TRAIL gene couldn't inhibit tumor growth in a nude mice HCC model. Mostly, HCC tissue and both HCC cell lines expressed survivin, whereas normal liver tissue did not express survivin. Treatment with antisence oligonucleotide enhanced sTRAIL-inducing apoptosis. IL-12 significantly augmented sTRAIL-inducing apoptosis and inhibited survivin expression.

CONCLUSIONSHCC cells are insensitive towards TRAIL-mediated apoptosis. Survivin may play a role in resistance to TRAIL-induced apoptosis in HCC, and antisence oligonucleotide could partly reverse the resistance to TRAIL-inducing apoptosis. IL-12 may sensitize HCC cells to TRAIL-induced apoptosis by preventing survivin. Combining gene therapy strategy such as combining gene therapy of TRAIL with IL-12 may be a promising maneuver to HCC.

Animals ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; Carcinoma, Hepatocellular ; pathology ; therapy ; Cell Line, Tumor ; Genetic Therapy ; Humans ; Inhibitor of Apoptosis Proteins ; Interleukin-12 ; administration & dosage ; genetics ; Liver Neoplasms ; pathology ; therapy ; Membrane Glycoproteins ; administration & dosage ; genetics ; Mice ; Mice, Nude ; Microtubule-Associated Proteins ; antagonists & inhibitors ; Neoplasm Proteins ; Recombinant Proteins ; administration & dosage ; TNF-Related Apoptosis-Inducing Ligand ; Transfection ; Tumor Necrosis Factor-alpha ; administration & dosage ; genetics