Aims—The T cell production of TNF-α and theimpact of this cytokine on intestinal T cell proliferation, migration,and cytotoxicity were studied.
Methods—Intestinal lymphocytes from normaljejunum were used. TNF-α production in culture supernates wasmeasured by enzyme linked immunosorbent assay (ELISA). Lymphocyteproliferation was measured using 3H thymidine uptake;migration, using transwell chambers; and cytotoxicity of HT-29 coloncancer cells, using the chromium-51 release assay.
Results—TNF-α was produced mainly by the CD8+ Tcells in the intraepithelial lymphocytes (IEL) and the CD4+ T cells inthe lamina propria lymphocytes in response to CD2 stimulation: 478(94)and 782 (136) pg/ml, respectively. TNF-α (1 ng/ml or greater) augmented proliferation of IEL in response to interleukin 2 (IL-2), IL-7, or antibody to CD3 due to increased activation that did notinvolve IL-2 production or receptor generation. Conversely, antibody toTNF-α reduced IEL proliferation in response to IL-2 or IL-7. TNF-αalso induced calcium mobilisation and chemokinesis (by 2.8 (0.5) foldover spontaneous migration). TNF-α had no effect on lymphokineactivated killer cell activity.
Conclusions—TNF-α increases the proliferationand migration of IEL, which may expand their number in the epithelium.
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Aims—To determine the effect of biliary drainageon plasma concentrations of TNF-α, its soluble circulating receptors(sTNFr), and other proinflammatory cytokines.
Methods—Plasma concentrations of TNF-α,sTNFr-P75, interleukin 6 (IL-6), and IL-1α were measured in 25 patients with malignant bile duct obstruction before and afterendoscopic stent insertion.
Results—Mean serum bilirubin was 157 µmol/lbefore stent insertion and 35.2 µmol/l one week post stent insertion.There was complete relief of jaundice in 77% of patients by fourweeks. Plasma concentrations of TNF-α and IL-1α were below thedetection limit of the assays in all samples. Median plasma sTNFr-P75in the cancer patients was 960 ng/l (range 400-6600) before stent insertion and remained unchanged at one and four weeks after stenting. Plasma sTNFr-P75 in cancer patients was significantly higher(p<0.01) than in healthy controls (250 (200-650) ng/l).Before stent insertion, plasma IL-6 concentrations were detectable(above 5 ng/l) in 17(68%) patients. After relief of biliaryobstruction IL-6 levels fell from a prestent median of 13.2 to lessthan 5 ng/l at one week after stent insertion. Plasma concentrations ofIL-6 were undetectable in 76% of patients at this time.
Conclusion—Activation of the TNF/sTNFr complex isunchanged after biliary drainage in patients with malignant bile ductobstruction. This may explain why preoperative drainage does notinfluence the high morbidity and mortality associated with surgery inthese patients.
Keywords:jaundice; tumour necrosis factor α; biliarydrainage; pancreatic cancer
相似文献Aims—To investigate whether PMN from patients withIBD or infectious colitis, respectively, secrete increased amounts ofpro-inflammatory cytokines and can be regulated by IL-10.
Methods—Secretion (ELISA) as well as correspondingmRNA levels (semiquantitative RT-PCR) of pro-inflammatory cytokines(IL-1β, TNF-α) and of IL-1 receptor antagonist were assessed inperipheral PMN.
Results—PMN from patients with IBD are primed tosecrete enhanced amounts of pro-inflammatory cytokines accompanied bydetection of corresponding mRNAs in comparison with normal controls.This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL-10 markedly inhibited pro-inflammatory cytokine secretion as well as corresponding mRNA concentrations.
Conclusions—PMN are an important source ofpro-inflammatory cytokines in patients with intestinal inflammation andcan be downregulated by IL-10.
Keywords:granulocytes; interleukin 1β; interleukin 10; inflammatory bowel disease; intestinal immunity; inflammation; neutrophils; tumour necrosis factor α
相似文献Aims—To investigate therelation between the cagA gene and the productionof various cytokine proteins using an enzyme linked immunosorbentassay (ELISA).
Patients and methods—In 184 patients,the cagA gene was detected by polymerase chain reaction(PCR), and levels of production of IL-1β, IL-6, IL-7, IL-8, IL-10,and tumour necrosis factor α (TNF-α) in antral biopsy specimenswere measured by ELISA.
Results—Mucosal levels of IL-1β, IL-6,IL-8, and TNF-α were significantly higher in H pyloripositive than in H pylori negative patients.Furthermore, the mucosal levels of IL-1β and IL-8 were significantly higher in specimens infected with cagApositive strains than in those infected with cagAnegative strains. In H pylori positivepatients, the mucosal level of IL-8 was closely correlated withthat of IL-1β (p<0.0001), and the mucosal level of IL-6was closely correlated with that of TNF-α (p<0.0001).
Conclusion—These findings suggest that theability to induce cytokines differs among the strains;cagA+ strains induce various kinds ofcytokines and may cause severe inflammation, whereascagA strains induce IL-8 and IL-1β onlyweakly and may cause only mild inflammation. However, as most patientsinfected with the cagA+ strains havegastritis, these strains may not be equivalent to ulcerogenic strains.
Keywords:cytokines; Helicobacter pylori; cagA gene; interleukin 8; interleukin 1β
相似文献Aims—To investigate the profiles of α and β chemokine secretion in colonic cell lines and their differentialmodulation by interferon γ (IFN-γ), a product of activated Tlymphocytes and natural killer cells.
Methods and results—HT29-19A, a model of theCl secretory crypt cell, exhibited a parallel secretionof the α chemokines IL-8 and GROα, which could be markedlyupregulated by tumour necrosis factor α (TNF-α) and IL-1β. Thesecells showed no significant expression of the β chemokines RANTES(regulated upon activation T cell expressed and secreted), MIP-1α(macrophage inflammatory protein 1α), and MCP-1 (monocyte chemotacticprotein 1) under these conditions, but IFN-γ in combination withTNF-α caused a dose dependent induction of RANTES and MCP-1secretion. This was accompanied by a marked increase of RANTES mRNA. Incontrast, IFN-γ had no significant effect on TNF-α stimulated IL-8secretion. Caco-2 cells, with features more typical of villusabsorptive cells, were relatively poor secretors of α chemokines butsecreted high levels of MCP-1 in response to IL-1β. IFN-γ did notinfluence α or β chemokine secretion in these cells.
Conclusions—These studies suggest that intestinalepithelial cells may produce chemokines capable of attracting bothneutrophils and monocytes. The ability of IFN-γ to activate theexpression of β chemokines preferentially could facilitate thedevelopment of chronic inflammatory infiltrates.
Keywords:inflammatory bowel disease; RANTES; interferongamma; chemokine
相似文献Aims—To examine the effects of glutaminesupplemented elemental diets on the potent inflammatory cytokinesinterleukin 8 (IL-8) and tumour necrosis factor α (TNF-α) intrinitrobenzene sulphonic acid (TNBS) induced colitis which presentswith both acute and chronic features of ulcerative colitis.
Methods—Sprague-Dawley rats were randomised intothree dietary groups and fed 20% casein (controls), or 20% caseinsupplemented with either 2% glutamine (2% Gln) or 4% glutamine (4%Gln). After two weeks they received intracolonic TNBS to inducecolitis.
Results—Both Gln groups of rats gained more weight thanthe control group (p<0.05) which had progressive weight loss. Colon weight, macroscopic, and microscopic damage scores for the Gln groupswere lower than in the control group (p<0.05). IL-8 and TNF-αconcentrations in inflamed colonic tissues were lower in the Gln groupsthan in the control group (p<0.05), and correlated well with diseaseseverity. Bacterial translocation was lower both in incidence (p<0.05)and in the number of colony forming units (p<0.05) for the Gln groups,than in the control group. With respect to all indices studied, the 4%Gln group performed better than did the 2% Gln group.
Conclusion—Prophylactic glutamine supplementationmodulates the inflammatory activities of IL-8 and TNF-α in TNBSinduced colitis.
Keywords:glutamine; trinitrobenzene sulphonic acid; inflammatory bowel disease; rats; interleukin 8; tumour necrosis factorα
相似文献Aims—To investigate the circulatingconcentrations of βhCG in patients with exocrine pancreaticadenocarcinoma and to examine its potential prognostic value.
Patients—Thirty six patients with exocrinepancreatic adenocarcinoma, 12 patients with chronic pancreatitis, and21 healthy volunteers were studied.
Methods—βhCG serum concentrations were detectedby the application of a radioimmunoassay technique.
Results—Fifteen of 36 patients with pancreaticadenocarcinoma and only one patient with chronic pancreatitis haddetectable plasma concentrations of βhCG (p<0.01). The patients withcirculating serum titres of βhCG had a worse outcome compared withthe group of βhCG negative patients: the difference was statisticallysignificant (p=0.01).
Conclusion—More than 40% of pancreatic exocrinetumours produce βhCG and its production is correlated with an adverseeffect on outcome.
Keywords:β-human chorionic gonadotropin; chorionicgonadotropin; pancreatic cancer; tumour marker; paraneoplasticsyndrome
相似文献Aims—To investigatethe state of nuclear factor-κB (NF-κB) in macrophages of rats withlethal pancreatitis, and to assess the effectiveness of pyrrolidinedithiocarbamate, an inhibitor of NF-κB, on the pathology and mortality.
Methods—Taurocholatepancreatitis was produced in rats, and the severity of the disease, themortality, and activation of NF-κB in peritoneal and alveolarmacrophages were compared in rats receiving pyrrolidine dithiocarbamate(PDTC) treatment and those that were not.
Results—Taurocholatepancreatitis produced massive necrosis, haemorrhage, and severeleucocyte infiltration in the pancreas as well as alveolar septalthickening in the lung. NF-κB was activated in peritoneal andalveolar macrophages six hours after pancreatitis induction.Pretreatment with PDTC dose-dependently attenuated the NF-κBactivation and improved the survival of the rats, although it did notaffect the early increase in serum amylase and histological findings.
Conclusions—Earlyblockage of NF-κB activation may be effective in reducing fataloutcome in severe acute pancreatitis.
Keywords:pancreatitis; multiple organ dysfunction; nuclearfactor-κB; pyrrolidine dithiocarbamate; macrophages; rat
相似文献Aims—To investigate plasma leptin concentrationsduring the time course of intestinal inflammation in different animal models.
Methods—Plasma leptin was measured at differenttime points in rats with trinitrobenzene sulphonic acid (TNBS) inducedcolitis, indomethacin induced ileitis, or endotoxic shock caused bylipopolysaccharide (LPS). Systemic TNF-α was also measured duringacute inflammation.
Results—Plasma leptin concentrations increasedfourfold eight hours after induction of TNBS colitis (p<0.0001) andtwofold after administration of ethanol alone (p<0.02). Plasma leptin responses throughout the first post-treatment day were correlated withmyeloperoxidase activity and gross damage scores. Similar leptinoverexpression was observed in indomethacin induced ileitis and in ratswith endotoxic shock. Plasma concentrations were lower in TNBS treatedrats than in controls on day 5 before reaching a similar concentrationon day 14. Anorexia and body weight loss were observed during the firstfour days post-TNBS. A significant increase in systemic TNF-α wasonly detected in LPS treated rats.
Conclusion—Elevated plasma leptin concentrations,correlated with the degree of inflammation and associated withanorexia, were induced in rats during the early stages of experimentalintestinal inflammation but proved transient; this might account fordiscrepancies in recent results concerning concentrations in patientswith inflammatory bowel diseases.
Keywords:leptin; inflammatory bowel disease; experimental ratintestinal inflammation; tumour necrosis factor; endotoxic shock; anorexia
相似文献Aims—To quantify interferon γ (IFN-γ) andinterleukin 4 (IL-4) secreting cells (SC) among human intraepithelial(IEL) and lamina propria (LPL) lymphocytes from the duodenum and rightcolon in non-pathological situations and in the absence of in vitro stimulation.
Patients—Duodenal and right colonic biopsyspecimens were obtained from patients with no inflammation of theintestinal mucosa.
Methods—Intraepithelial and lamina propria cellsuspensions were assayed for numbers of cells spontaneously secretingIFN-γ and IL-4 by a two site reverse enzyme linked immunospottechnique (ELISPOT).
Results—The relatively high proportion ofduodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very lownumbers of spontaneously IFN-γ SC and the absence of spontaneouslyIL-4 SC among peripheral blood mononuclear cells. In the basal state,both IFN-γ and IL-4 were mainly produced by CD4+ cells.Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in thebasal state, and 0.1% secreted IL-4.
Conclusions—Compared with peripheral lymphocytessubstantial proportions of intestinal epithelial and lamina proprialymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokinesare probably involved in the normal homoeostasis of the humanintestinal mucosa. Disturbances in their secretion could play a role inthe pathogenesis of gastrointestinal diseases.
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