The
interleukin-6 (IL-6) receptor, which exists as membrane-bound and soluble forms, plays critical roles in the immune response. The soluble
IL-6 receptor (sIL6R) has been identified as a potential therapeutic target for preventing
coronary heart disease. However, little is known about the role of this receptor during
viral infection. In this study, we show that sIL6R, but not
IL-6, is induced by
viral infection via the
cyclooxygenase-2 pathway. Interestingly, sIL6R, but not
IL-6, exhibited extensive
antiviral activity against
DNA and RNA viruses, including hepatitis B virus, influenza virus, human enterovirus 71, and
vesicular stomatitis virus. No synergistic effects on
antiviral action were observed by combining sIL6R and
IL-6. Furthermore, sIL6R mediated
antiviral action via the p28 pathway and induced
alpha interferon (IFN-α) by promoting the nuclear translocation of
IFN regulatory factor 3 (IRF3) and NF-κB, which led to the activation of downstream IFN effectors, including
2',5'-oligoadenylate synthetase (OAS),
double-stranded RNA-dependent
protein kinase (PKR), and myxovirus resistance
protein (Mx). Thus, our results demonstrate that sIL6R, but not
IL-6, plays an important role in the host
antiviral response.