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Effect of IL‐6 knockout on susceptibility to HSV‐1 respiratory infection and intrinsic macrophage anti‐viral resistance in mice
Author(s) -
Murphy E Angela,
Davis J Mark,
Carmichael Martin D,
Ghaffar Abdul,
Mayer Eugene P
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a213-c
Subject(s) - immunology , virus , macrophage , herpes simplex virus , respiratory system , knockout mouse , virology , biology , titer , medicine , receptor , in vitro , biochemistry
Cytokines play important roles in the mechanisms of disease development. Interleukin‐6 (IL‐6) has been 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 in mice 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 anti‐viral resistance to HSV‐1. Control C57BL/6 IL‐6 +/+ mice and IL‐6 gene knockout mice (IL‐6−/−) were intranasally inoculated with 50μl 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 48h post‐infection and lungs were analyzed for viral titers using a standard plaque assay. Peritoneal macrophages were obtained from additional mice and assayed for anti‐viral resistance to HSV‐1 We found that IL‐6 −/− increased morbidity by 84%, mortality by 84% and symptom severity score on days 8 through 10 (P<0.05). IL‐6−/− increased virus titers in the lung 4 fold (P<0.05) and resulted in a decrease in intrinsic macrophage anti‐viral resistance (P<0.05). Results indicate that IL‐6 plays an important role in susceptibility to respiratory infection in mice, which may be mediated by its effect on macrophage anti‐viral resistance.

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