Modulation of TH1 and TH2 cytokine production with the immune response modifiers, R-848 and imiquimod

Cell Immunol. 1999 Jan 10;191(1):10-9. 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-alpha. Results from the present study demonstrate that R-848 and imiquimod are capable of inducing interleukin-12 and interferon-gamma in mouse and human cell cultures. Both CD4(+) and CD8(+) T lymphocytes were responsible for producing IFN-gamma following stimulation with R-848. Macrophages were required for induction of interferon-gamma by R-848 and the cytokines IFN-alpha 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-alpha. 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.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Aminoquinolines / pharmacology*
  • Animals
  • Cytokines / biosynthesis*
  • Humans
  • Imiquimod
  • 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


  • Adjuvants, Immunologic
  • Aminoquinolines
  • Cytokines
  • Interferon-alpha
  • Interleukin-5
  • S 28463
  • Interleukin-12
  • Interferon-gamma
  • Imiquimod