In vitro analysis of the factors contributing to the antiviral state induced by a plasmid encoding the viral haemorrhagic septicaemia virus glycoprotein G in transfected trout cells

We have found out that transfection of the RTG-2 cell line with the viral haemorrhagic septicaemia virus (VHSV) glycoprotein G (G_VHSV)-coding plasmid induces an anti-VHSV state, similar to that induced by poly I:C. Taking the advantage of the constitutive expression of toll-like receptor 9 gene (tlr9) in RTG-2 cells, we have investigated whether this antiviral state was induced by the cytosine-phosphodiester-guanine (CpG) motifs present in the plasmid DNA, by the endogenous expression of G_VHSV protein or by both elements. For that, we have analysed the expression profile of the rainbow trout tlr9 and several genes related to TLR9-mediated immune response in the absence or presence of a lysosomotropic drug that specifically blocks TLR9-CpG DNA interaction. The results suggested that the high levels of cell protection conferred by a plasmid encoding G_VHSV gene are due to G_VHSV rather than to the CpG motifs within plasmid DNA. Therefore, plasmid DNA might not play a key role in the immune response elicited by DNA vaccines or perhaps other receptors instead TLR9 could be implicated in CpG motifs recognition and signalling. In addition, since RTG-2 cells express tlr9 gene, this cell line could be a good tool for screening TLR9 agonists, such as the immunomodulatory oligonucleotides (IMOs), as fish DNA vaccine adjuvants.  

Therapie der juvenilen idiopathischen Arthritis (JIA) mit Zytokinantagonisten

Juvenile idiopathic arthritis is a chronic inflammatory disease with uncertain outcome. Patients may suffer from severe joint damage leading to mutilations as well as from extra-articular manifestations. Prognosis is variable and depends in part on the number of affected joints and the occurrence of extra-articular manifestations. Treatment regimes should take this into account. Pharmacomedical treatment strategies include the application of nonsteroidal antirheumatics, corticosteroids, sulfasalazine, and immunosuppressive substances. However, of the latter only methotrexate has been shown in controlled trials to be effective. Other immunosuppressive drugs such as azathioprine, cyclosporine A, and leflunomide have not yet been investigated sufficiently. In addition, there is no scientific basis for the application of gold salts or (hydroxy)chloroquine. New therapeutic biologic agents, notably the tumor necrosis factor inhibitors, have achieved dramatic improvements also in patients with severe, as yet intractable disease. However, until now randomized, placebo-controlled trials have been performed for etanercept only. Dramatic improvement was accompanied by low toxicity. Infections as well as the development of autoimmune diseases have been shown to be the major potential side effects. Long-term toxicity still has to be evaluated. Treatment with other biopharmaceuticals such as infliximab, IL-1Ra, anti-IL-6 receptor antibodies, and further cytokine antagonists remains experimental.