Effect of IL-6 Deficiency on Susceptibility to HSV-1 Respiratory Infection and Intrinsic Macrophage Antiviral Resistance

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 µL of a standardized dose (3.2 × 105) 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−/− in...