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

AbstractCytokines 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.
AuthorsE Angela Murphy, J Mark Davis, Adrienne S Brown, Martin D Carmichael, Abdul Ghaffar, Eugene P Mayer (Affiliation: Division of Applied Physiology, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29208, USA.)
JournalJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 28 Issue 10 Pg. 589-95 (Oct 2008) ISSN: 1557-7465 United States
PMID18778200 (Publication Type: Journal Article)