Humans ; Arthritis, Psoriatic/drug therapy* ; Interleukin-17 ; Interleukin Inhibitors ; Antirheumatic Agents/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Interleukin-23/therapeutic use*

OBJECTIVETo explore the effect of combination therapy of tetramethylpyrazine (TMP) with methotrexate (MTX) on collagen induced arthritis (CIA) rats.

METHODSTotally 55 male SD rats were stratified by body weight. Nine of them were randomly recruited as the normal control group. The rest 46 were immunized with type II bovine collagen (C II) for establishing rheumatoid arthritis (RA) model. Forty successfully modeled rats were randomly divided into 4 groups according to swollen toe degree, i.e., the CIA group, the TMP group, the MTX group, and the TMP plus MTX group, 10 in each group. Rats in the MTX group were administered with MTX (1. 2 mg/kg) , once per week for 4 continuous weeks. Those in the TMP group were administered with 40 mg/kg TMP, once per day for 10 continuous days, and then discontinued for 7 successive days, and continued for another 10 successive days. Rats in the TMP plus MTX group were administered with a mixture of equal dose MTX and TMP, and when MTX was discontinue, TMP was administered according to the way in the TMP group. Equal volume of saline solution was given to rats in the normal control group and the CIA group. Clinical parameters including ankle width (mediolateral diameter) and hindpaw swelling were measured at day 0, 4, 11, 18, and 26 after treatment. Rats were sacrificed 28 days after treatment, their knee joints and ankle joints were collected for pathological analyses. Serum levels of IL-1β, IL-6, and IL-17A were detected by ELISA. Changes of fibrinogen (FIB) and platelet aggregation rate (PAg) were detected.

RESULTSCompared with the normal control group, the ankle width and hindpaw swelling increased significantly (P < 0.01), contents of FIB and PAg increased obviously (P < 0.05, P < 0.01), serum levels of IL-1β, IL-6, and IL-17 increased remarkably (P <0. 01) in the CIA group. Obvious cell proliferation, inflammatory cell infiltration, hyperemia and edema of synovial tissues could be seen. Pannus formed and immerged in cartilages, resulting in necrosis. Compared with the model group, changes of ankle width and hindpaw swelling were all alleviated in each medicated group (P <0. 05, P <0. 01). Of them, the effect was superior in the MTX group to that of the TMP group and the MTX plus TMP group (P < 0.05, P < 0.01). Contents of FIB, serum levels of IL-1β and IL-6 decreased significantly in the MTX group (P < 0.05). Contents of FIB, serum levels of IL-1β and IL-6 decreased significantly in the TMP group and the MTX plus TMP group (P < 0.05). Besides, serum levels of FIB and IL-6 were obviously lower in the MTX plus TMP group than in the TMP group and the MTX group (P < 0.01). Levels of PAg and IL-17A were more significantly lowered in the TMP group than in the MTX plus TMP group and the MTX group. Pathological changes could be alleviated in each medicated group, with the optimal effect obtained in the MTX plus TMP group.

CONCLUSIONCombination of TMP with MTX could significantly ameliorate inflammatory reactions and FIB contents of CIA rats.

Animals ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Cattle ; Collagen Type II ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Hemorheology ; Interleukin-17 ; Interleukin-1beta ; Interleukin-6 ; Male ; Methotrexate ; therapeutic use ; Pyrazines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane

OBJECTIVETo study the effects of Zhengqing Fengtongning Tablet (ZFT) and methotrexate (MTX) on the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), and interleukin 17 (IL-17) in collagen-induced arthritis (CIA) rats, thus addressing their bone protection.

METHODSThe CIA rat model was established by intradermally injecting type II collagen emulsion from the rats' back and tail. Totally 28 successfully modeled rats [with the arthritis index (AI) more than 2] were randomly divided into the model group, the Chinese medicine (CM) treatment group, the MTX group, and the ZFT + MTX treatment group, 7 rats in each group. Another 7 rats were recruited as the normal control group. Rats were administered from the 7th day of modeling. Rats in the MTX group were treated with MTX at 3.8 mg/kg once a week. Those in the CM group were treated with ZFT at the daily dose of 130 mg/kg, once a day. Those in the ZFT + MTX treatment group were treated with both MTX (at 3.8 mg/kg once a week) and ZFT (at the daily dose of 130 mg/kg, once a day). Those in the model group and the normal control group were administered with normal saline of the equal volume by gastrogavage. All the intervention lasted for 26 days. The destruction of joints in the four limbs were observed using X-ray. The AI was recorded. The expression levels of serum OPG, RANKL, and IL-17 were detected at the end of the experiment.

RESULTSDuring the whole process, all rats except those in the model group were in a good condition. On the 21st day of modeling the AI of all rats reached the peak, but it decreased after treatment. Compared with the model group, the AI decreased in the CM treatment group, the MTX group, and the ZFT + MTX treatment group with statistical difference (P < 0.05). Compared with the model group, the OPG increased and RANKL decreased in the MTX group; the OPG and OPG/RANKL increased in the CM treatment group; the OPG, RANKL, and OPG/RANKL increased, and IL-17 decreased in the ZFT + MTX treatment group, all showing statistical difference (P < 0.05). Compared with the MTX and the ZFT + MTX treatment group, OPG/RANKL increased and IL-17 decreased in the ZFT + MTX treatment group (both P < 0.05).

CONCLUSIONZFT + MTX could synergistically elevate peripheral OPG/RANKL and down-regulate IL-17 in CIA model rats.

Animals ; Arthritis, Experimental ; blood ; chemically induced ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interleukin-17 ; blood ; Methotrexate ; pharmacology ; therapeutic use ; Osteoprotegerin ; blood ; RANK Ligand ; blood ; Rats

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.
Ammonia/therapeutic use* ; Animals ; Anti-Inflammatory Agents/therapeutic use* ; Cyclooxygenase 2 ; Dendrobium/chemistry* ; Interleukin-17/therapeutic use* ; Interleukin-6 ; NF-kappa B/metabolism* ; Pharyngitis/drug therapy* ; Plant Extracts/chemistry* ; Polysaccharides/pharmacology* ; Rats ; Tumor Necrosis Factor-alpha ; Water

OBJECTIVETo study the effect of bitter-cold herbs easing dampness method (BCHEDM) plus Sanhuang Yilong Decoction (SYD) combined with methotrexate (MTX) on expression levels of interleukin-1 (IL-1), IL-6, and IL-17 in rheumatoid arthritis (RA) patients of accumulated dampness-heat syndrome (ADHS).

METHODSFrom January 2011 to January 2013 recruited were 90 RA inpatients of ADHS at Department of Integrative Medicine on Rheumatoid Disease, General Hospital of Chengdu Military Region. They were assigned to the treatment group (45 cases) and the control group (45 cases) according to the random digit table produced by SPSS 11.5 Software. Patients in the treatment group were treated by heavy bitter-cold herbs plus SYD combined with MTX, while those in the control group were treated by MTX alone. Expressional levels of IL-1, IL-6, and IL-17 in serum were detected by enzyme linked immunosorbent assay (ELISA) before treatment, at week 2 and 4 after treatment. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score in 28 joints (DAS28) were detected as well.

RESULTSAfter two or four weeks of treatment, ESR, CRP, and DAS28 decreased more in the treatment group than in the control group with statistical difference (P < 0.05, P < 0.01). After four weeks of treatment, IL-1, IL-6, IL-17, ESR, CRP, and DAS28 in the treatment group were all lower than before treatment and those of the control group at corresponding time points with statistical difference (P < 0.01).

CONCLUSIONSYD combined MTX could play roles of improving inflammatory indices within 2 weeks, and inhibiting the expression of IL-1, IL-6, and IL-17 within 4 weeks.

Arthritis, Rheumatoid ; blood ; drug therapy ; immunology ; Blood Sedimentation ; C-Reactive Protein ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Hot Temperature ; Humans ; Interleukin-1 ; blood ; Interleukin-17 ; blood ; Interleukin-6 ; blood ; Methotrexate ; therapeutic use ; Syndrome ; Treatment Outcome

OBJECTIVE: To investigate the effect of interleukin-17A (IL-17A) on chemosensitivity of ovarian cancer cells to cisplatin (DDP) and explore the mechanism in light of autophagy regulation. METHODS: Ovarian cancer SKOV3 cells cultured RESULTS: DDP increased the expression of IL-17RA in ovarian cancer SKOV3 cells. Treatment with IL-17A significantly reduced the susceptibility of SKOV3 cells to cisplatin-induced apoptosis ( CONCLUSIONS IL-17A/IL-17RA can decrease chemosensitivity of SKOV3 cells to DDP by upregulating DDP-induced autophagy.
Antineoplastic Agents/therapeutic use* ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Cisplatin/pharmacology* ; Drug Resistance, Neoplasm/drug effects* ; Female ; Humans ; Interleukin-17/pharmacology* ; Ovarian Neoplasms/drug therapy* ; Receptors, Interleukin-17

OBJECTIVETo detect the expression level of interleukin 17 (IL-17) in the plasma and colonic mucosa of patients with ulcerative colitis (UC), and to explore the synergistic mechanism of qingchang huashi recipe (QHR) combined with Mesalazine.

METHODSRecruited were 24 mild or moderate UC patients of damp-heat inner accumulation syndrome (DHIAS). Their samples of intestinal tissues were histologically graded. They were assigned to the combination group and the Western medicine (WM) group, 12 in each group. Besides, another 12 healthy volunteers were recruited as the healthy control group. QHR combined Mesalazine were given to patients in the combination group, while those in the WM group took Mesalazine. The therapeutic course for all was 3 months. By the end of treatment the expression level of IL-17 in the plasma and colonic mucosa was detected using ELISA. The infiltration of IL-17 in the intestinal mucosal tissue was detected by immunohistochemical SP method.

RESULTSThe expression level of IL-17 in the plasma and colonic mucosa was significantly higher in UC patients than in healthy controls (P <0. 05). The higher the histological grading the higher the expression level. The expression level of IL-17 in plasma and colonic tissues decreased after treatment in the two treatment groups (P < 0.05). Besides, the expression level of IL-17 was lower in the combination group than in the WM group (P <0.05).

CONCLUSIONQHR combined Mesalazine could synergically enhance the effect and effectively inhibit intestinal inflammation through down-regulating the expression of IL-17.

Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Immunologic Factors ; metabolism ; Inflammation ; metabolism ; Interleukin-17 ; metabolism ; Intestinal Mucosa ; drug effects ; Intestines ; metabolism ; Mesalamine ; therapeutic use

OBJECTIVE: To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania. METHODS: Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA. RESULTS: The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05). CONCLUSION Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.
Aggression/drug effects* ; Antipsychotic Agents/therapeutic use* ; Biomarkers/blood* ; Bipolar Disorder/drug therapy* ; Case-Control Studies ; Diagnostic and Statistical Manual of Mental Disorders ; Double-Blind Method ; Humans ; Interleukin-17/metabolism* ; Lithium Compounds/therapeutic use* ; Quetiapine Fumarate/therapeutic use* ; Treatment Outcome

The aim of this study was to detect the rate of T-helper (Th)17 cells and interleukin (IL)-17 level in peripheral blood of patients with primary immune thrombocytopenia (ITP) and to explore their clinical significance. The proportion of Th17 cells from 48 patients with ITP and 28 healthy controls was detected by flow cytometry, and the IL-17 level was evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that the percentage of Th17 cells in ITP group was (1.40 ± 1.35)%, which was significantly higher than that in healthy control group (P < 0.05), but in the glucocorticoid hormone-treated group it was significantly lower than that in treated group without glucocorticoid hormone(P < 0.05). The level of IL-17 expressed by Th17 cells in ITP patients was (19.624 ± 5.187) pg/ml, which was higher than that in the healthy control group (P < 0.05), it was lower in the glucocorticoid hormone treated group than that in treated group without glucocorticoid hormone, but there was no statistically significant difference between the glucocorticoid treated and treated group without glucocorticoid hormone (P > 0.05). It is concluded that the Th17 cells may involve in the pathogenesis of ITP, and the glucocorticoid hormone probably plays a therapeutic role through inhibiting Th17 cells.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Interleukin-17 ; metabolism ; Male ; Middle Aged ; Th17 Cells ; metabolism ; Thrombocytopenia ; drug therapy ; metabolism ; Young Adult

OBJECTIVES: To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance. METHODS: A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD. RESULTS: Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001). CONCLUSIONS Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.
Humans ; Child ; Infant ; Aged, 80 and over ; Immunoglobulins, Intravenous/therapeutic use* ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Interleukin-17 ; Clinical Relevance ; Prospective Studies ; C-Reactive Protein/analysis* ; Retrospective Studies