Involvement of virus-induced interferon production in IgG autoantibody-mediated anemia

Infection with viruses, such as the lactate dehydrogenase-elevating virus (LDV), is known to trigger the onset of autoimmune anemia through the enhancement of the phagocytosis of autoantibody-opsonized erythrocytes by activated macrophages. Type I interferon receptor-deficient mice show enhanced anemia, which suggests a protective effect of these cytokines, partly through the control of type II interferon production. The development of anemia requires the expression of Fc gamma receptors (Fc gamma R) I, III, and IV. Whereas LDV infection decreases Fc gamma R III expression, it enhances Fc gamma R I and IV expression in wild-type animals. The LDV-associated increase in the expression of Fc gamma R I and IV is largely reduced in type I interferon receptor-deficient mice, through both type II interferon-dependent and -independent mechanisms. Thus, the regulation of the expression of Fc gamma R I and IV, but not III, by interferons may partly explain the exacerbating effect of LDV infection on anemia that results from the enhanced phagocytosis of IgG autoantibody-opsonized erythrocytes.Functional Genomics of Systemic Disorder

TLR7 activation by LDV / R848 (Resiquimod) prevents acute graft versus host disease and cooperates with anti-IL-27 antibody for optimal protection

Graft-versus-host-disease remains an important complication of allogeneic hematopoietic cell transfer. We studied immune suppression by LDV/R848-TLR7 stimulation in acute GVHD mouse models. Our results have shown that TLR7 activation inhibits cDCs and allo responsiveness of T cells. Both inhibitions are dependent on type I IFN. This suppressive effect seems to hamper the GVHD initiation without affecting long-lasting implantation of donor T cells. In addition, GVHD prevention is associated with a decrease of inflammatory cytokine production and a reduction of organ lesions. We have also found that donor and host Treg cell numbers were increased in recipient mice and that their elimination compromised survival and exacerbated morbidity in R848-treated mice. When aGVHD was more severe, an anti-IL-27 blocking antibody was necessary to optimize the R848 protection by an upregulation Treg cell level. We conclude that R848-TLR7 stimulation modulates multiple aspects of GVHD and offers potential for safe allogeneic cell transplantation that can be further optimized by IL-27 inhibition.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201

Novel antibodies that selectively block mouse IL-12 enable the re-evaluation of the role of IL-12 in immune protection and pathology

The dimeric cytokine IL-12 is important in the control of various infections but also contributes to the pathology of certain diseases making it a potential target for therapy. However, its specific inhibition with antibodies is complicated by the fact that its two subunits are present in other cytokines: p40 in IL-23 and p35 in IL-35. This has led to erroneous conclusions like the alleged implication of IL-12 in experimental autoimmune encephalomyelitis (EAE). Here, we report the development of a mouse anti-mouse IL-12 vaccine and the production of monoclonal antibodies (mAbs) that do not react with p40 or p35 (in IL-35) but specifically recognize and functionally inhibit the IL-12 heterodimer. Using one of these mAbs, MM12A1.6, that strongly inhibited IFN-γ production and LPS-induced septic shock after viral infection, we demonstrate the critical role played by IL-12 in the rejection of male skin graft by female C57BL/6 syngeneic recipients and in the clearance of an immunogenic mastocytoma tumor variant by DBA/2 mice, but not in a parent to F1 immune aggression model nor in MOG-induced EAE, which was clearly prevented by anti-p40 mAb C17.8. Given this selective inhibition of IL-12, these mAbs provide new options for reassessing IL-12 function in vivo

Communautarisering, decentralisatie, deconcentratie en deregulering

Three points will be considered in the following pages. To begin with, there will be a short sketch of the political and socio-economic situation which helped to start the move towards decentralization and deregulation. Second, there will be a brief review of the main forms that decentralization and deregulation take in the different levels of education. The account will be confined to basic, secondary and higher non-uni-versity education. Third, by way of example there will be a review of the way principals of secondary schools are using their increased autonomystatus: publishe

Dexamethasone Bovine Pharmacokinetics

peer reviewedDexamethasone phosphate (DXM-PHO) is an ester which is quickly hydrolysed by the bovine and the dexamethasone (DXM) plasma half-life was 5.16 h. It has been demonstrated that 54 h after DXM-PHO injection, DXM concentrations were lower than 0.1 mglml. Tritiated dexamethasone was also administered twice to an another young bull for metabolite investigation. The elapsed time required to recover, in plasma, half of the radioactivity injected was 8.8 h. Radioactivity recovery in the urine reached 36.4% and 22.6% for the first and the second injections respectively

Synthesis of dexamethasone related compounds. Purification by preparative liquid chromatography and high performance liquid chromatography-mass spectrometry characterization.

peer reviewe

Applications Of Chromatographic And Spectrometric Techniques To The Study Of Dexamethasone Related-Compounds

peer reviewedA methodology for the analysis of dexamethasone and related compounds is proposed. Nine corticoids (corticosteroids) have been separated by TLC and by normalphase HPLC. The optimization of the HPLC separation is performed on a diol column and with a n-hexane/isopropanol (80:20) mobile phase. Mass spectrometry is used to elucidate the nature of the compounds isolated from illicit drug formulations and to confirm the structure of synthesised derivatives from the parent dexamethasone