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Objective:To investigate the effects of IL-18BP blockade on apoptosis of synovial cell in IL-18 induced Collagen-induced-arthritis(CIA) in mice and its possible mechanism.Methods: CIA mice were established by freund′s complete adjuvant,and divided into 5 groups:normal group,CIA model group,IL-18-CIA group,MTX group and IL-18BP group,each for 10,total 50 mice.The expression of Fas and FasL in the synovial tissue of the left posterior ankle joint taken from each group were detected by immunohistochemistry analysis.Results: IL-18BP group compared with the model group,the mice of joint swelling was inhibited,the expression level of Fas and FasL increased significantly,the difference was statistically significant (P<0.01);IL-18BP group has a significant curative effect and basically recovered to normal level(P<0.05).Conclusion: IL-18BP can promote the apoptosis of synoviocytes by regulating the expression of apoptosis genes Fas and FasL,which is helpful for the treatment of rheumatoid arthritis.
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Objective:To study the effects of andrographolide on the expression of IL-18 related cytokines by peripheral blood monocytes.Methods:After treatment of andrographolide in different concentrations on LPS stimulated human peripheral blood mononuclear cells (PBMC) and LPS+IFN-γ/IL-4 activated magnetic bead-sorted monocytes (PBM),the transcription level of IL-18,IL-18BP,IL-18Rα and IL-18Rβ was detected by real-time RT-PCR;and secreted IL-18,IL-18BP and IL-1β,IL-1Rα by PBM was detected with ELISA.Results:Andrographolide regulated the transcription of IL-18 and IL-18BP in a dose-and time-dependent effect.Andrographolide up-regulated the transcription of IL-18BP in LPS stimulated PBMC,and increased the ratio of IL-18BP/IL-18.The ratio of IL-18BP/IL-18 rose from 9.60 to 214 in LPS+IFNγ activated PBM,and IL-1Rα/IL-1β declined from 9 200 to 6 520 in IL-4 activated PBM by andrographolide treatment.Conclusion:Andrographolide can regulate IL-18 related gene transcription and expression in activated peripheral blood monocytes,and inhibit the excessive expression of IL-18 during inflammation.
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Objective:To investigate the effect and the mechanism of interleukin-18 binding protein(IL-18BP) on acute graft-versus-host disease(aGVHD) in allogeneic bone marrow transplantation(allo-BMT) in mice.Methods:C57BL/6 recipient mice irradiated with 60Co were randomly divided into 2 groups: group A and B and were transfused with BALB/c donor cells.After transplantation recipient mice in group A were treated with NS subcutaneously daily from day 0 to day 5 and recipient mice in group B with 1 ?g IL-18BP,separately.The severity of aGVHD was evaluated in the two groups.Concentrations of IFN-?,IL-2,IL-4 and IL-10 were measured using enzyme-linked immunosorbent assay(ELISA).Results:aGVHD response was more severe in group A than that in group B.The serum concentrations of IFN-? and IL-2 in group A were higher than that in group B,while the serum concentrations of IL-10 and IL-4 were lower than that in group B.Conclusion:①IL-18BP can decrese aGVHD response;②That IL-18BP can promote the differentiation of CD4~+T cells into CD4~+Th2 cells,that is promoted by IL-18BP might be one of the mechanisms of decreasing aGVHD.