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Interleukin-18 is an inactive precursor which lacks a signal peptide,it has a role inregulating retinal pathological angiogenesis.It also inhibits experimental choroidal neovascularization (CNV)via interferon-γand thrombospondin-1.Currently little is known about its mechanisms of inhibition forCNV,may be speculated to be due to effects of anti-angiogenesis,down-regulates vascular permeability andlower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial celland epithelial cells.Exogenous administration of mature recombinant interleukin-18 has no adverse effect onretinal pigment epithelial cell viability.In addition,the anti-VEGF role of interleukin-18 is tested to be safeand effective for humans.Interleukin-18 alone or in combination with anti-VEGF shows to be a goodprospect for improving the prognosis of experimental CNV.However,more large clinical studies arerequired to confirm the exact efficacy of interleukin-18 for CNV.
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Objective To explore the association of suprapatellar pouch effusion with knee pain and serum levels of interleukin (IL)-6,IL-17,IL-23 in patients with knee osteoarthritis measured by magnetic resonance imaging (MRI).Methods 204 patients with knee osteoarthritis were enrolled into the study.Suprapatellar pouch effusion was measured by OSIRIS in both grade (0-3) and maximum area (cm2).Serum IL-6,IL-17,IL-23 were measured.Knee pain was assessed by Western Ontario and McMasters osteoarthritis index (WOMAC) questionnaire and Lequesne index.Characteristics of patients were recorded and body mass index (BMI) was calculated.Student t test or Chi-square test was used to compare means or proportions.Multivariable linear regression or logistic regression was used to determine risk factors (α=0.05).Results ① In the 204 patients [mean age (55±8) years,86.3％ were females],the prevalence of physiologic effusion (≤ 1) was 47.9％ while moderate or larger (≥2) effusion was 52.1％.② The age,labour intensity,serum levels of uric acid (sUA) and Lequesne index of higher grade effusion group were higher (P＜0.05) compared with lower grade effusion group.③ Suprapatellar pouch effusion maximum area was positively correlated with age (r=0.208,P=0.006),BMI (r=0.171,P=0.027) and labour intensity (r=0.189,P=0.013).④ Adjusted for age,gender and BMI,the results of Logistic regression analysis showed that:suprapatellar pouch effusion grades were positively correlated with Lequesne index [OR=1.120,95％CI(1.011,1.241),P=0.029] and negatively correlated with IL-23 [OR=0.768,95％CI (0.598,0.986),P=0.038].Suprapatellar pouch effusion was not independently associated with WOMAC index,IL-6 and IL-17.Conclusion The prevalence of suprapatellar pouch pathological effusion is 52.1％ in knee osteoarthritis.Suprapatellar pouch effusions is positively correlated with knee pain (Lequesne index) and negatively conrelated with IL-23.
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ObjectiveThe expression and significance of interleukin(IL)-17 in a murine model of experimental systemic sclerosis(SSc) was studied and its correlation with transforming growth factor-beta 1 (TGF-β1) was explored.Methods Thirty female BALB/c mice were randomly divided into 3 groups,including a control group, bleomycin(BLM) injection for 4 weeks group(model 1 group) and a termination injection of BLM 4 weeks group(model 2 group).The pathological changes of skin and lung were detected.The mRNA expressions of IL-17A,RORγt,TGF-β1 mRNA were evaluated by real-time PCR.Enzyme linked immunosorbent assay was used to measure the levels of IL-17 and TGF-β1 in the serum and bronchoalveolar lavage fluid(BALF).Comparisons among groups were performed by variance analysis.ResultsSkin and lung of the model groups showed evident inflammatory cell infiltration and increased deposition of collagen fibers.The score of dermal inflammation and lung fibrosis was significantly higher in the model 1 and model 2 groups (2.5±0.8,3.0±1.8), (2.4±0.8,3.1±1.2) as compared to that of the control group (0.9±0.7,0.9±1.0),(F=12.19,8.367,25.11,4.641; all P＜0.05).The amount of hydroxyproline was markedly increased in the model groups than in the control group.Compared with those of the control group,the mRNA levels of IL-17A,RORγt,TGF- 31 in the skin and lung of the model 1 group were higher.The levels of IL-17 in serum and BALF of the model 1 group was significantly increased and the levels of TGF- β1 were increased in BALF and decreased in the serum (all P＜0.05).The mRNA levels of IL-17A in skin and lung had a positive correlation with the mRNA levels of TGF- β1,score of dermal inflammation and lung fibrosis.The levels of IL-17 in serum had a positive correlation with hydroxyproline of the skin and lung.ConclusionIL-17 may participate in systemic immune-mediated inflammation and changes of skin and lung in SSc and when combined with TGF-β1 togetter will cause damage to skin and lung in SSc.
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Objective To investigate the effect of corticotrophin-releasing factor (CRF) on the regulation of Toll-like receptor 4/NF-κB signaling pathway expression in human intestinal epithelial cell line HT-29. Methods HT-29 cells were divided into four groups, normal control group, LPS group (LPS 20 μg/ml stimulated for 24 h), CRF group (CRF 20 ng/ml stimulated 24 h) and CRF+ LPS group (CRF incubated for 12 h then changed to LPS for another 12 h). After stimulation, the expression of TLR4 mRNA of each group was examined by reverse transcriptase polymerase chain reaction (RT-PCR). Total cell protein were extracted and the expression of TLR4 and NFκB p65 at protein level were detected by western blotting.Cell culture supernatant was collected and the secretion of interleukin-8 was detected by enzyme-linked immunoasorbent assay (ELISA). Results The expression of TLR4 in LPS group at mRNA and protein level were 0.31±0.04 and 0.48±0.17,there was no significant difference compared with normal control group (0.28±0.02 and 0.45±0.12,t＝0.216 and 0.712 , P＞0.05 ). In CRF group which were 1.05±0.06 and1. 08±0.21, significantly higher than normal control group (t＝3.721 and 3.802, P＜0.05). In CRF+LPS group which were 1.68±0.05 and 1.81±0. 18,significantly higher than CRF group (t＝4. 816 and 3. 918, P＜0.05).The results of NF-κB p65 expression at protein level and interleukin-8 expression of cell culture supernatant were consistent with the results of TLR4 expression at mRNA and protein level.Conclusion CRF not only activate TLR4/NF-κB signaling pathway in human intestinal epithelial cell,but enhance the reaction of intestinal epithelial cell to LPS as well, which resulting in increased interleukin-8 secretion.
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Objective To investigate the effects of arsenic trioxide (ATO) on the expression of autoan-tibody and interleukin (IL)-10 IL-12 in MRL/lpr mice. Methods MRL/lpr mice wereseparated into 3 different groups. The 3 groups received arsenic trioxide (ATO, 0.4 mg·kg~(-1)·d~(-1)), cyclophosphamide (CTX,50 mg/kg) and sodium chloride (NS, volume weight-determined) abdominal injection respee-tively. The treatment stopped 2 months later. Afterwards, the rates of CD3~+(T) cells, CD3~+CD4~+(Th) cells and the CD3~+CD4~+cells which produced IL-10 and IL-12 were detected using single-cell measurement of intr-acellular eytokines by flow cytometry after polyclonal stimulation with PMA and ionomycin for 4 hours in 5% CO_(2.)Serum levels of IL 10 and IL-12 were assessed using the Mouse cytokines ELISA Kit. One-way ANOVA LSD test and paires t test were used for statistical analysis.Results ①The level of anti-dsDNA antibody after treatment was 0.92±0.06, while it was 1.14±0.58 before treatment. So the ds-DNA antibody level was significantly decreased in ATO group (P<0.01), while it was dramatically increased in the NS groups (P<0.05) after the treatment;②ATO group had significantly less CD3~+ cells and CD3~+CD4~+ cells[(44±4)% and (20±4)%]compared withNS group [(59±5)%and(30±3)%](P<0.01).③The serum level of IL-12 in the ATO group was (84±12) pg/ml,while it was (103±13)pg/ml in the NS group (P=0.018).④The intracellular levels of IL-10 and IL-12 produced by CD3~+CD4~+ (Th) cells in the ATO group were ( 1.5±0.4)% and (2.43±0.42)%, which was significantly lower than those in the NS group respectively (2.5±0.5)% and (3.24±0.40)%(P<0.01). Conclusion Arsenic trioxide can reduce the production of anti-dsDNA antibody,inhibit the activation and proliferation of both T cells and Th subsets in the MRLApr mice, and hence decrease the serum levels of IL-12 and the levels of IL-10, IL-12 produced by Th cells.
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Objective To investigate the effects of andrographolide on the expressions of Th1 cytokine [interferon (IFN)-γ] mRNA and Th2 cytokines [interleukin (ID-4, IL-10] mRNA of peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis B (CHB) and its anti-hepatitis B virus (HBV) activity. Methods PBMCs from CHB patients were cultured with 10 mg/L andrographolide (experimental group) or 0.1% DMSO (control group). HepG2. 2. 15 cells were stimulated with andrographolide of different concentrations (experimental group) or adefovir (control group). The expressions of IFN-γ mRNA, IL-4 mRNA and IL-10 mRNA of PBMCs and the replication of HBV DNA in HepG2. 2. 15 cell line were detected by fluorescence quantitative PCR. Results The expression of IFN-γ mRNA in PBMCs cultured with 10 mg/L andrographolide for 16 h was higher than that in control group (Z=-2. 78, P=0. 05), and the expressions of IL-4 and IL-10mRNA in experimental group were lower than control group (Z= -3. 82, P<0. 01), while the ratio of IFN-γ/IL-4 mRNA was higher than control group (Z= - 3. 82, P<0. 01). Andrographolide with different concentrations had no effect on the replication of HBV DNA in HepG2. 2.15 cells ((=11. 88, P>0.05). However, adefovir had inhibitory effect on the replication of HBV DNA (t =15. 95,P< 0. 05). Conclusion Andrographolide can regulate the expressions of IFN-γ mRNA, IL-4 mRNA and IL-10 mRNA in PBMCs from CHB patients and improve Thl/Th2 balance, while it has no effect on the replication of HBV DNA.
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Objective To investigate the expression of interleukin-17 in the salivary gland and peripheral blood of patients with primary Sjogren's syndrome (pSS).Methods Biopsy specimens of labial glands were collected from 30 patients and 5 controls.Immunohistochemistry examination was conducted to detect IL-17 expression cells (Th-17),while CD45RO and CD20 were tested by using monoclonal antibodies.IL-17 levels were assessed by ELISA in 30 pSS patients and 20 healthy controls.Results Th-17 cell numbers in the salivary glands of pSS patients with few infiltrating lymphocytes were lower than that with massive infiltrating lymphocytes (15±5 vs 21±8,P＜0.05).However,the percentage of Th-17 positive cells over the total infiltrating lymphocytes in the salivary glands of pSS patients with few infiltrating lymph-ocytes was higher than that with massive infiltrating lymphocytes (P＜0.05).There was no expression of IL-17 in the controls.The distribution pattern of Th-17 was shown that Th-17 cells were distributed evenly in the salivary glands of pSS patients with few infiltrating lymphocytes,but only appeared in the periphery zone of massive or focal infiltration in the glands of pSS patients with massive infiltrating lymphocytes.The amount of Th-17 positive cells were associated with the disease activity which was evaluated by levels of erythrocyte sedimentation rate (r=0.557,P＜0.05).There was no significant differ-ence in IL-17 levels of peripheral blood between patients with pSS and normal controls.Conclusion The results of this study have shown that Th-17 is expressed in the salivary glands of patients with pSS,which indicates that IL-17 may play an important role in the pathogenesis of salivary gland destruction.
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Objective To investigate the effects of alpha-melanocyte-stimulating hormone (alpha-MSH) on the production of tumor necrosis factor-alpha (TNF-alpha) and intedeukin-10 (IL-10) by peri-pheral blood monohuclear cells (PBMCs) from patients with psoriasis vulgaris. Methods Heparinized peri-pheral blood was obtained from 20 patients with psoriasis vulgaris and 10 healthy human controls. PBMCs were isolated, cultured in complete medium, and stimulated with phytohemagglutinin (PHA) alone, the com-bination of PHA and various concentrations of alpha-MSH, or nothing. After another 48-hour culture, ELISA and real-time PCR were performed to measure the secretion levels of TNF-alpha and IL-10 in the super-natants of cultured PBMCs as well as the mRNA expression levels of TNF-alpha and IL-10 in PBMCs. Results The secretion level of TNF-alpha in the supematants of patient-derived PBMCs stimulated by nothing or PHA alone was significantly higher than that from normal control-derived PBMCs (329.87 ± 99.33 ng/L vs 116.95 ± 37.15 ng/L, 1756.01 ± 183.60 ng/L vs 1287.30 ± 152.36 ng/L, both P<0.01). alpha-MSH of all tested concentrations (10-13, 10-11, 10-7,mol/L) could inhibit the secretion of TNF-alpha by PBMCs com-pared with PHA alone (all P < 0.01), and the maximum effective concentration was 10-13 mol/L. On the con-Wary, a significant decrease was observed in the secretion level of IL-10 in the supematants of patient-derived PBMCs stimulated by nothing or PHA alone compared with normal control-derived PBMCs (P <0.05 or 0.01). Moreover, the secretion of IL-10 by PBMCs was promoted by alpha-MSH of all tested con-centrations (P < 0.01 or 0.05), with the maximum effective concentration being 10-13 mol/L (P < 0.01). The alpha-MSH of 10-13 mol/L down-regulated the mRNA expression of TNF-alpha (P < 0.001), but up-regnlated that of IL-10 (P < 0.001) in PHA-stimulated PBMCs from patients. Conclusion alpha-MSH can regulate the production of TNF-alpha and IL-10 by PHA-stimulated PBMCs from patients with psoriasis vulgaris.
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Objective To investigate the association between interleukin-23 receptor (IL-23R) gene rs1343151 single nucleotide polymorphism and ankylosing spondylitis (AS) in Chinese Han patients. Methods The genotypes of IL-23R SNP was detected in 104 Chinese AS patients and 95 ethnically matched blood donors by TaqMan probe assays. The allele and genotype frequencies and risk factors of AS were analyzed by Chi-square test in both groups. Results The rs 1343151 genotypes in AS patients consisted of homozygote C/C (90.4%),C/T (9.6%), while The rs1343151 genotypes in the controls were. composed of C/C (91.6%), C/T (8.4%). No significant difference was found in the distribution of rs1343151 genotypes between these two groups (x2=0.086, P>0.05). The frequency of rs1343151 allele in AS patients was also not significantly increased when compared with the control group (x2 =0.082,P>0.05). Conclusion There may be no association between the IL-23R gene rs1343151 SNP and ankylosing spondylitis in Chinese Hart population.
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Objective To investigate the effect of adenoviral-mediated interleukin-10 (IL-10) gene transfection on systemic inflammatory responses in a rat model of ventilator-induced lung injury. Methods Thirty adult male SD rats weighing 200-220 g were randomly divided into 5 groups (n=6 each): group Ⅰ control (group C); group Ⅱ adenovirus without IL-IO gene + 2 h mechanical ventilation (MV) (group B, ); group II1 adenoviruswithout IL-IO gene + 4 h MV (group B_2); group Ⅳ adenovirus with IL-10 gene + 2 h MV (group A_1) and group Ⅴ adenovirus with IL-10 gene + 4 h MV (group A_2). In group Ⅱ-Ⅴ the animals were mechanically ventilated (airway pressure = 25 cm H_2 O) and adenovirus was injected into right ventricle at 48 h before MV. Blood samples were taken from abdominal aorta at the end of 2 h or 4 h MV for determination of serum IL-8 and IL-10 concentrations. The animals were then killed. The pulmonary specimens were obtained for examination of ultrastructure with light and electron microscope. Results Mechanical ventilation significantly increased serum IL-8 and IL-IO concentrations in a duration-dependent manner in group Ⅱ-Ⅴ as compared with group C. Trans-pulmonary administration of adenoviraI-mediated interleukin-10 gene significantly decreased serum IL-8 concentration and increased serum IL-10 concentration and reduced ventilator-induced lung injury alter MV in group A_1 and A_2 as compared with group B_1 and B_2. Conclusion Adenoviml-madiated IL-10 gene transfection can attenuate the systemic inflammatory response and reduce ventilator-induced lung injury.
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Objective To investigate the relationship between bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and child bacterial pneumonia. Methods BALF levels of IL-6, IL-8 were detected by enzyme linked immunosorbent assay (ELISA) in 26 patients with bacterial pneumonia and 14 controls. Neutrophils and alveolar macrophages (AMs) of BALF were examined. Results BALF levels of IL-6, IL-8, total cell count and neutrophils of child bacterial pneumonia before treatment were significantly higher than those of pneumonia after treatment and controls (P<0.01). BALF levels of IL-6, IL-8 were significantly higher in Gram-negative infection than those in Gram-positive infection (P<0.01). BALF level of IL-6 showed positive correlation with AMs in pneumonia (r=0.7615, P<0.01). BALF level of IL-8 was correlated positively with neutrophils and AMs respectively in pneumonia (r=0.8956, r=0.6018, P<0.01). Conclusions IL-6 and IL-8 play the roles in the development of airway inflammation in child bacterial pneumonia. Detection of BALF levels of IL-6 and IL-8 is valuable to predict the state of child bacterial pneumonia.
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Objective To observe the effect of octreotide acetate on plasma ETX and serum inflammatory cytokine of the rabbit with hepatic ischcmia reperfusion injury. Methods Pringle's maneuver rabbit hepatic ischemia-repeffusion models were established. 24 adult New Zealand rabbits were random divided into equal 3 groups: sham operative group(group A), iacbemia reperfusion group(group B)and octreotide acetate preconditioning group(group C). Endotoxin (ETX) in the plasma, tumor necrosis factor-alpha (TNF-α) and intcdeukin-1beta (IL-1β) were detected in every rabbit at the time before iachemia (T1), 30min after ischemia (T2), 30min (T3) and 120min (T4) after reperfusion. Results From T2 to T4, the ETX in group B and C were higher than that in group A (P < 0.05), the ETX of group C were lower than that in group B (P<0.05). From T2 to T4, the TNF-α of group B and C were higher than that of group A(P<0.05). From T3 to T4 the TNF-α of group C were higher than that of group A(P<0.05). From T2 to T4,the IL-1β of group B and group C were higher than that of group A(P<0.05), and the IL-1β of group C were lower than that of group B (P<0.05). Conclusion Octreotide acetate can decrease plasma ETX and down-regulate inflammation factors, such as TNFαand IL-1β, in serum of the rabbit with hepatic iacbe-mia-reperfusion injury, which may be the protective mechanism of oetreotide acetate on rabbit hepatic isehemia-reperfusiun injury.
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0.05) and decrease to higher than normal in CH and in 4 cases of SH (P
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The Change in interleukin-2 (IL-2) production of splenocyte and its relationship with suppressor T cell (Ts) were studied in mice after trauma. The results showed that IL-2 production was reduced, number of Ts was increased and activity of Ts correlated with reduced IL-2 production. Removal of Ts from splenocyte improved IL-2 production in traumatized mice. It is suggested that Ts is activated after trauma, resulting in impaired IL-2 production.