The Expression Of IL-22in Behcet Disease,Vogt-Koyanagi-Harada Syndrome And The Effects Of IL-23, Dexamethasone And Cyclosporin A On Production Of IL-22

Part ⅠIncreased expression of IL-22is associated with diseaseactivity in Behcet disease and smallvascular inflammationObjectiveInterleukin (IL)-22has been reported to be involved in the development ofautoimmune diseases. This study aimed to analyze the expression andpotential role of IL-22in the pathogenesis of Behcet disease(BD).MethodsThe levels of IL-22in the sera or the supernatants of cultured peripheralblood mononuclear cells(PBMCs) and CD4~+T cells were detected byenzyme-linked immunosorbent assay(ELISA).Flow cytometry was used toevaluate the frequencies of IL-22–producing CD4~+/CD8~+T cells andIL-12~+IL-17~+CD4~+Tcells. IL-22mRNA in the erythema nodosum was examined using rea-ltime quantitative RT-PCR. Correlations of IL-22supernatant levels were sought with clinical features, serological markersfactors.ResultsThe BD patients with actived uveitis showed a significantly higherexpression of IL-22in the supernatants of stimulated PBMCs and CD4~+TCells.Increased frequency of IL-22-producing CD4~+T cells andIL-22,IL-17double positve CD4~+T cells was also found in these patients.there was no significant difference regarding the frequency ofIL-22-positive CD8~+T cells among BD patients and healthy controls. Theresults showed only a part of IL-22-postive CD4~+T cells was also postivefor IL-17in BD patients healthy controls (21%-27%), more than half ofIL-22-producing cells was negative for IL-17. IL-22mRNA expression waselavated in erythema nodosum.‘High IL-22levels in the supernatants ofstimulated PBMCs`were correlated with cells in the anteriorchamber,retinal vasculitis and erythama nodosum.ConclusionsThese results showed that IL-22was associated with the activity of BD andvascular inflammation, suggesting it may be invloved in the pathogenesisof Behcet disease. Part ⅡThe effect of IL-23, Dexamethasone and Cyclosporin A on theproduction of IL-22by CD4~+T cells and PBMCs cells inBehcet diseaseObjectiveTo study the effect of IL-23, Dexamethasone and Cyclosporin A on theproduction of IL-22by T cells in Behcet disease.Methodsseven healthy controls and Seven BD patients with active uveitis wereincluded in this project. PBMCs were prepared by Ficoll-Hypaquedensity-gradient centrifugation. CD4~+T cells were purified by MACS usinga human CD4~+T cell isolation kit. PBMCs culture contained4groups:a.without any stimulations, b.with anti-CD3and anti-CD8antibodies c.with anti-CD3,anti-CD8antibodies and rhIL-23. CD4~+Tcells culturecontained6groups: a.without any stimulations, b.with anti-CD3andanti-CD8antibodies c. with b group and Dexamethasone, d.with b groupand Cyclosporin A, e. with c group and rhIL-23, f.with d group andrhIL-23.ResultstionWe observed that rhIL-23could promote the production of IL-22byCD4~+T cells,and the elevation is significantly higher in BD patients with active uveitis.Both Dexamethasone and Cyclosporin A could inhibit IL-22production by PBMCs from Behcet patients and normal controls in a dosedependent manner. Both DEX and CsA couldn`t completely inhibite theproduction of IL-22. DEX could suppresse70%of IL-22production at100ng/ml., and CsA could suppresse80%of IL-22production at10ng/ml.ConculsionThe increasd expression of IL-22in BD patients may be due to theinduction of IL-23, and there may be a IL-23/IL-22passway in Behcetdisease Corticosteroids and Cyclosporin A could inhibit the production ofIL-22. Part ⅢIncreased expression of IL-22is associated with diseaseactivity in Vogt-Koyanagi-Harada syndromeObjectiveInterleukin (IL)-22has been reported to be involved in the development ofautoimmune diseases. This study aimed to analyze the expression andpotential role of IL-22in the pathogenesis of Vogt-Koyanagi-Haradasyndrome(VKH).MethodsThe levels of IL-22in the sera or the supernatants of cultured PBMCs and CD4~+T cells were detected by enzyme-linked immunosorbentassay(ELISA).Flow cytometry was used to evaluate the frequencies ofIL-22–producing CD4~+T cells. Correlations of IL-22supernatant levelswere sought with clinical features, serological markers factors.ResultsThere was no significant difference with regards to IL-22serum levelsamong BD patients with active uveitis,BD patients without active uveitis,normal controls.The VKH patients with actived uveitis showed asignificantly higher expression of IL-22in the supernatants of stimulatedPBMCsand CD4~+T Cells. Increased frequency of IL-22-producing CD4~+T cells was also found in these patients.However there was no significantdifference regarding the frequency of IL-22-positive CD8~+T cells amongBD patients and healthy controls. The results showed only a part ofIL-22-postive CD4~+T cells was also postive for IL-17in BD patientshealthy controls, more than half of IL-22-producing cells was negative forIL-17.‘High IL-22levels in the supernatants of stimulated PBMCs’ werecorrelated with mutton fat keratic precipitates and cells in the anteriorchamber.ConclusionsThese results showed that IL-22was associated with the activity of VKH,suggesting it may be invloved in the pathogenesis of VHK. Part ⅣThe effect of IL-23, Dexamethasone and Cyclosporin A onthe production of IL-22by CD4~+T cells and PBMCs inVogt-Koyanagi-Harada syndromeObjectiveTo study the effect of IL-23, Dexamethasone and Cyclosporin A on theproduction of IL-22by T cells in VKH syndrome.MethodsNine healthy controls and nine VKH patients with active uveitis wereincluded in this project. PBMCs were prepared by Ficoll-Hypaquedensity-gradient centrifugation. CD4~+T cells were purified by MACS usinga human CD4~+T cell isolation kit. PBMCs culture contained4groups:a.without any stimulations, b.with anti-CD3and anti-CD8antibodies c.with anti-CD3,anti-CD8antibodies and rhIL-23. CD4~+Tcells culturecontained5groups: a.without any stimulations, b.with anti-CD3andanti-CD8antibodies c. with b group and Dexamethasone, d.with b groupand Cyclosporin A, e. with b group and Dexamethasone, Cyclosporin A.ResultsWe observed that rhIL-23could promote IL-22production by CD4~+Tcells,and this ability is significantly stronger in VKH patients with activeuveitis.Both Dexamethasone and Cyclosporin A could inhibit IL-22 production on PBMCs from VKH patients and normal controls,and theinhibitory effect is in a dose dependent manner.ConculsionThe increasd expression of IL-22may be due to the induction of IL-23,and there may be a IL-23/IL-22passway in VKH syndrome.Corticosteroidsand Cyclosporin A could inhibit the production of IL-22by PBMCs.