Modulation of TH1 and TH2 Cytokine Production with the Immune Response Modifiers, R-848 and Imiquimod

• Published in: Cellular immunology 1999-01, Vol.191 (1), p.10-19
• Main Authors: Wagner, Tamara L., Ahonen, Cory L., Couture, Aimee M., Gibson, Sheila J., Miller, Richard L., Smith, Rose M., Reiter, Michael J., Vasilakos, John P., Tomai, Mark A.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Aminoquinolines - pharmacology; Animals; Cytokines - biosynthesis; Humans; Interferon-alpha - biosynthesis; Interferon-gamma - biosynthesis; Interleukin-12 - biosynthesis; Interleukin-5 - biosynthesis; Male; Mice; Mice, Inbred BALB C; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - metabolism
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1998.1406

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.