Thioredoxin (TRX) is a small redox-active
protein with
anti-oxidant effect and redox-regulating functions. Using TRX transgenic (Tg) mice in which human TRX is overexpressed systemically under the control of
beta-actin promoter, the effects of influenza virus
infection were examined in TRX Tg mice and wild type C57BL/6 mice. (1) Median lethal dose (LD50) against influenza virus
infection in wild-type C57BL/6 mice was 10(-5.3) dilution, while that of TRX Tg mice was 10(-4.2) dilution. Thus, TRX Tg mice were more resistant against the
virus infection than wild-type mice. (2) The
body weights of wild-type mice 7 days after
infection with a sublethal dose of the virus (10(-6) dilution) decreased significantly, whereas those of TRX Tg mice increased slightly. (3) Histopathology of the lung at 3 weeks after sublethal
infection of influenza virus showed that severe alveolar or bronchiolar destruction was observed in wild-type mice, while mild
viral pneumonia was seen in the TRX Tg mice. (4) Local (
IgA) and systemic (
IgG) antibody productions against influenza virus
hemagglutinin in mice surviving 3 weeks after
infection were similar between wild-type and TRX Tg mice. These results indicate that overexpression of TRX in Tg mice suppresses the inflammatory overshoot of
viral pneumonia caused by influenza virus
infection, resulting in the reduction of mortality without affecting the host's systemic immune responses to the
infection. TRX may play some important roles in regulating the inflammatory process in the primary host defense against
infection.