Our previous studies have shown that vitamin A (VA) status is associated with antiviral immunity and pathogenic conditions in enterovirus 71 (EV71)-infected children. In the present study, we established an in vitro model to investigate the effects and potential mechanism of the antiviral activity of VA. Human monocytic U937 cells were cultured in vitro and infected with EV71. All-trans-retinoic acid (ATRA), the active metabolite of VA, and Ro 41-5253, a retinoic acid receptor-α (RAR-α) antagonist, were used as the experimental treatment agents. The percentage of EV71-infected cells and apoptosis induced by EV71 were determined using flow cytometry. The level of interferon-α (IFN-α) in the supernatants of the cultures was detected using ELISA. The expression of retinoid-induced gene I (RIG-I) and its downstream genes was examined with real-time quantitative PCR. The results indicated that ATRA reduced the percentage of EV71-infected cells and protected cells against EV71-induced apoptosis. Correspondingly, ATRA increased the production of IFN-α one of the most important antiviral cytokines, at both mRNA and protein levels in EV71-infected cells. In addition, the expression of RIG-I mRNA and its downstream genes was up-regulated by ATRA in EV71-infected cells. Ro 41-5253 abrogated the inhibitory effects of ATRA on EV71. The present findings suggest that ATRA is an interferon-inducing agent with antiviral activity against EV71 in vitro and that its actions are mediated at least in part by RAR-α activity and the RIG-I signalling pathway.

Acute toxoplasmosis was induced in mice, and interferon (IFN) production in serum and by spleen cells was evaluated during the infection period. Interferon was characterized by acid-treatment and anti-IFN-α/β neutralization. In order to verify the correlation between the unusual aspects of the IFN production and the induction of immunosuppression, splenocyte mitogen responsiveness was investigated concomitantly to IFN synthesis. The activity of Toxoplasma-induced serum IFN-α/β increased gradually throughout all post-infection days, but IFN-γ was not detected in the systemic circulation at any time during the infection. It was also observed that IFN-α/β production and the capacity to produce IFN-γ by spleen cells were closely and inversely correlated. As the infection progressed, more IFN-α/β was produced, and the ability of spleen cells to produce IFN-γ decreased. The observation that Toxoplasma-infected mice were concomitantly immunosuppressed (as documented by mitogen unresponsiveness and defective IFN-γ production) in direct correlation to IFN-α/β production, suggests that such IFN-α/β production is an important factor associated with acute toxoplasmosis-induced immunosuppression.

An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression.

Objectives: To assess the clinical-effectiveness and cost-effectiveness of pegylated interferon alfa (2a and 2b) combined with ribavirin in previously untreated patients with moderate to severe chronic hepatitis C, compared with the current standard treatment, which is nonpegylated interferon alfa combined with ribavirin.

Methods: Systematic review and economic evaluation. A sensitive search strategy was applied to several electronic bibliographic databases. Relevant studies were critically appraised and meta-analyzed. A hypothetical cohort of 1,000 patients entered a Markov model and were followed up for a more than 30-year period to predict natural history, duration spent in each health state, and treatment costs.

Results: Two fully published Phase III randomized controlled trials were included. Methodological quality was generally good. Dual therapy with pegylated interferon was significantly more effective than nonpegylated dual therapy with a pooled sustained virological response rate (SVR) of 55 percent (95 percent confidence interval [CI], 52–58 percent) compared with 46 percent (95 percent CI, 43–49 percent). The pooled relative risk of remaining infected was 0.83 (95 percent CI, 0.76–0.91 percent). Genotype was the strongest predictor of outcome, with SVRs in patients with the more responsive genotypes 2 and 3 reaching up to 80 percent. The incremental cost per quality-adjusted life year (QALY) for pegylated dual therapy compared with nonpegylated dual therapy was £12,123. The cost per QALY remained under £30,000 for most patient subgroups and in sensitivity analyses.

Conclusions: Pegylated interferon is clinically effective, represents good value for the money, and is a significant advance in the treatment of this insidious disease.