title: Effect of IL-6 deficiency on susceptibility to HSV-1 respiratory infection and intrinsic macrophage antiviral resistance.
abstract: Cytokines play important roles in the mechanisms of disease development. Interleukin-6 (IL-6) is associated with clearance of herpes simplex virus (HSV) infections and in virus-induced immunopathology. However, the importance of IL-6 in host defense against HSV-1 respiratory infection is unknown. This study tested the effect of knockout mice deficient for IL-6 on susceptibility to HSV-1 respiratory infection and on intrinsic macrophage antiviral resistance to HSV-1. Control C57BL/6 IL-6+/+ mice and IL-6 knockout mice (IL-6-/-) were intranasally inoculated with 50 microL of a standardized dose (3.2 x 10(5)) of HSV-1. Morbidity, mortality, and symptom severity were monitored for 21 days. A subset of mice was sacrificed at 48-h postinfection and lungs were analyzed for viral titers. Peritoneal macrophages were obtained from a third set of mice and assayed for antiviral resistance to HSV-1. IL-6-/- increased morbidity by 84%, mortality by 84%, and symptom severity score on days 7.5 through 11 (p < 0.05). IL-6-/- increased virus titers in the lung 4-fold (p < 0.01) and resulted in a decrease in macrophage antiviral resistance (p < 0.001). Results indicate that IL-6 plays an important role in susceptibility to respiratory infection in mice, which may be mediated at least in part by its effect on macrophage antiviral resistance.
authors.affiliation: Division of Applied Physiology, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29208, USA.
authors.forename: E Angela
authors.initials: EA
authors.lastname: Murphy
authors.forename: J Mark
authors.initials: JM
authors.lastname: Davis
authors.forename: Adrienne S
authors.initials: AS
authors.lastname: Brown
authors.forename: Martin D
authors.initials: MD
authors.lastname: Carmichael
authors.forename: Abdul
authors.initials: A
authors.lastname: Ghaffar
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Mayer
mesh_terms: D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology*; D006561:Herpes Simplex / Q000276:immunology* / Q000401:mortality / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D015850:Interleukin-6 / Q000172:deficiency* / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019562:Viral Load
chemical_list: D015850:Interleukin-6