Search

Abstract: It has been reported that treatment with tricin (4′,5,7-trihydroxy-3′,5′-dimethoxyflavone), a derivative of Sasa albo-marginata, after human cytomegalovirus (HCMV) infection significantly suppressed both infectious virus production and HCMV replication in the human embryonic fibroblast cell line MRC-5. In this paper, we examined the mechanisms for the anti-HCMV effects of tricin in MRC-5 cells. Exposure of fibroblasts to tricin inhibited infectious HCMV production, with concomitant decreases in levels of transcripts of the CXC chemokine IFN-inducible T cell alpha chemoattractant (I-TAC or CXCL11) gene. We also found that the transcripts of the HCMV immediate early (IE) gene and replication of HCMV were lower in CXCL11 gene-knockdown cells. These results suggest that tricin is a novel compound with potential anti-HCMV activity and that CXCL11 is one of the chemokines involved in HCMV replication. In addition, it is possible that CXCL11 is the one of the targets of tricin. [Copyright &y& Elsevier]

Patients with chronic hepatitis C virus (HCV) can develop systemic cryoglobulinemic vasculitis. Combination of pegylatedinterferon α and ribavirin is the first-line treatment of this condition. However, in case of severe or life-threatening manifestations, absence of a virological response, or autonomized vasculitis, immunotherapy (alone or in addition to the antiviral regimen) is necessary. Rituximab is to date the only biologic with a sufficient level of evidence to support its use in this indication. Several studies have demonstrated that rituximab is highly effective when cryoglobulinaemic vasculitis is refractory to antiviral regimen, that association of rituximab with antiviral regimen may induce a better and faster clinical remission, and, recently, that rituximab is more efficient than traditional immunosuppressive treatments. Some issues with regard to the optimal dose of rituximab or its use as maintenance treatment remain unsolved. Interestingly, in balance with this anti-inflammatory strategy, a recent pilot study reported the significant expansion of circulating regulatory T lymphocytes with concomitant clinical improvement in patients with refractory HCV-induced cryoglobulinaemic vasculitis using low dose of subcutaneous interleukin-2. This paper provides an updated overview on the place of immunotherapy, especially biologics, in the management of HCV-induced cryoglobulinaemic vasculitis. [ABSTRACT FROM AUTHOR]

Recommended treatment of chronic hepatitis B with interferon-a and/or nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic vaccination or immunotherapies may be an innovative strategy to overcome virus persistence. Vaccination with commercially available HBV vaccines in patients did not result in effective control of HBV infection, suggesting that new formulations of therapeutic vaccines are needed. The woodchuck (Marmota monax) is a useful preclinical model for developing the new therapeutic approaches in chronic hepadnaviral infections. Several innovative approaches combining antiviral treatments with nucleos(t)ide analogues, DNA vaccines, and protein vaccines were tested in the woodchuck model. In this paper we summarize the available data concerning therapeutic immunization and gene therapy using recombinant viral vectors approaches in woodchucks, which show encouraging results. In addition, we present potential innovations in immunomodulatory strategies to be evaluated in this animal model. [ABSTRACT FROM AUTHOR]

This paper examines helper T-cell responses and antibody titres and isotypes following immunization with a peptide antigen in association with three different adjuvants. B10.A mice were primed with pigeon cytochrome c fragment 81-104 in association with the adjuvants complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA) and alum. Strong antibody responses, dominated by IgG1, were observed upon priming with CFA and IFA. In contrast, priming with alum induced a weak antibody response with little or no detectable antigen-specific IgG1. These differences did not correlate with differences in T-cell priming, as immunization with peptide in association with all three adjuvants induced comparable T-cell proliferative responses and frequencies of antigen-specific cells. In addition, no significant differences in iiiterleukin-2 (IL-2), interferon-gamma (IFN-γ) and IL-4 production could be found, suggesting that the adjuvants did not differentially affect Th1 and Th2 cells. [ABSTRACT FROM AUTHOR]