Author/Authors :
Wagner، نويسنده , , Tamara L. and Ahonen، نويسنده , , Cory L. and Couture، نويسنده , , Aimee M. and Gibson، نويسنده , , Sheila J. and Miller، نويسنده , , Richard L. and Smith، نويسنده , , Rose M. and Reiter، نويسنده , , Michael J. and Vasilakos، نويسنده , , John P. and Tomai، نويسنده , , Mark A.، نويسنده ,
Abstract :
Cytokines produced by antigen-presenting cells are known to affect the development and cytokine profile of T cells. The immune response modifiers imiquimod and R-848 were previously shown to stimulate human and mouse cultures to secrete interferon-α. Results from the present study demonstrate that R-848 and imiquimod are capable of inducing interleukin-12 and interferon-γ in mouse and human cell cultures. Both CD4+and CD8+T lymphocytes were responsible for producing IFN-γ following stimulation with R-848. Macrophages were required for induction of interferon-γ by R-848 and the cytokines IFN-α and IL-12 mediated this response. R-848 and imiquimod were also found to inhibit IL-4 and IL-5 production in mouse and human culture systems. The inhibition of IL-5 in response to R-848 is seen in cultures containing CD4+lymphocytes and macrophages and is mediated in part by IFN-α. These data suggest that imiquimod and R-848 may have clinical utility in diseases where cell-mediated immune responses are important and in diseases associated with overexpression of IL-4 or IL-5 such as atopic disease.
