Effect of IL-6 deficiency on susceptibility to HSV-1 respiratory infection and intrinsic macrophage antiviral resistance

• Published in: Journal of interferon & cytokine research Vol. 28; no. 10; p. 589
• Main Authors: Murphy, E Angela, Davis, J Mark, Brown, Adrienne S, Carmichael, Martin D, Ghaffar, Abdul, Mayer, Eugene P
• Format: Journal Article
• Language: English
• Published: United States 01-10-2008
• Subjects: Animals; Disease Susceptibility - immunology; Herpes Simplex - immunology; Herpes Simplex - mortality; Herpes Simplex - virology; Herpesvirus 1, Human - immunology; Interleukin-6 - deficiency; Interleukin-6 - immunology; Macrophages - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Viral Load
• ISSN: 1557-7465
• DOI: 10.1089/jir.2007.0103

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.