Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the antiviral activities of three recombinant human interferons (IFN-alph2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-gamma and IFN-beta were both highly active and reduced virus yields by 2 log (EC(99)) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-alpha2a (EC(99)> 1250 IU/ml) was at least 120 times less active than IFN-beta; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-alpha2a, our data suggest that IFN-beta should in preference be evaluated in the clinic.
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PMID:Recombinant Interferons beta and gamma have a higher antiviral activity than interferon-alpha in coxsackievirus B3-infected carrier state cultures of human myocardial fibroblasts. 916 21

Interferon (IFN)-beta has a more than 120-fold higher antiviral activity than the closely related IFN-alpha in human myocardial fibroblasts infected with the cardiotropic enterovirus coxsackievirus B3 (CVB3). CVB3 replication induces interleukin (IL)-6 and IL-8 expression in myocardial fibroblasts, and suppresses the expression of monocyte chemoattractant protein-1 (MCP-1). We investigated whether the higher antiviral activity of IFN-beta compared to IFN-alpha was a result of a suppression of IL-8 expression by IFN-beta since previous studies had indicated that IL-8 stimulates enterovirus replication. Human myocardial fibroblasts were treated with either IFN-alpha, IFN-beta or IFN-gamma (0, 10, 100, or 1,000 IU/ml) and the concentrations of IL-6, IL-8 and MCP-1 were measured in culture supernatants by immunoassays. Both IFN-beta and IFN-gamma reduced IL-6 and IL-8 expression significantly. In addition, neutralization of IL-8 in culture supernatants of myocardial fibroblasts using a monoclonal antibody demonstrated a significant reduction of CVB3 titers. Antiproliferative effects of all three IFNs were very low (<30% with 1,000 IU/ml), indicating that the suppression IL-6 and IL-8 was not related to cytotoxicity. MCP-1 expression was increased only by high concentrations of IFN-gamma (1,000 IU/ml). By contrast, IFN-alpha had no significant effect on IL-6, IL-8 and MCP-1 expression. In conclusion, suppression of IL-8 expression is an "immuno-modulating" feature of IFN-beta in human myocardial fibroblasts, which is similar to the activity of IFN-gamma. This feature of IFN-beta contributes to its high antiviral activity against CVB3 and may be useful in the treatment of enteroviral heart disease.
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PMID:Interferons in enteroviral heart disease: modulation of cytokine expression and antiviral activity. 1368 Feb 16