title: Evaluation of the immunomodulatory and antiviral effects of the cytokine combination IFN-α and IL-7 in the lymphocytic choriomeningitis virus and Friend retrovirus mouse infection models.
abstract: Existing therapies for chronic viral infections are still suboptimal or have considerable side effects, so new therapeutic strategies need to be developed. One option is to boost the host's immune response with cytokines. We have recently shown in an acute ex vivo HIV infection model that co-administration of interferon (IFN)-α and interleukin (IL)-7 allows us to combine the potent anti-HIV activity of IFN-α with the beneficial effects of IL-7 on T-cell survival and function. Here we evaluated the effect of combining IFN-α and IL-7 on viral replication in vivo in the chronic lymphocytic choriomeningitis virus (LCMV) and acute Friend retrovirus (FV) infection models. In the chronic LCMV model, cytokine treatment was started during the early replication phase (i.e., on day 7 post-infection [pi]). Under the experimental conditions used, exogenous IFN-α inhibited FV replication, but had no effect on viral replication in the LCMV model. There was no therapeutic benefit of IL-7 either alone or in combination with IFN-α in either of the two infection models. In the LCMV model, dose-dependent effects of the cytokine combination on T-cell phenotype/function were observed. It is possible that these effects would translate into antiviral activity in re-challenged mice. It is also possible that another type of IFN-α/β or induction of endogenous IFN-α/β alone or in combination with IL-7 would have antiviral activity in the LCMV model. Furthermore, we cannot exclude that some effect on viral titers would have been seen at later time points not investigated here (i.e., beyond day 34 pi). Finally, IFN-α/IL-7 may inhibit the replication of other viruses. Thus it might be worth testing these cytokines in other in vivo models of chronic viral infections.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland. annette.audige@usz.ch
authors.forename: Annette
authors.initials: A
authors.lastname: Audigé
authors.forename: Ursula
authors.initials: U
authors.lastname: Hofer
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.forename: Maries
authors.initials: M
authors.lastname: van den Broek
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Speck
mesh_terms: D000208:Acute Disease; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D015851:Interleukin-7 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D008216:Lymphocytic Choriomeningitis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012190:Retroviridae / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D015851:Interleukin-7