CYTOKINE INDUCTION IN MICE BY THE IMMUNOMODULATOR IMIQUIMOD

Imiquimod has been identified as a potent antiviral and antitumor agen t in animal models. The biological activity associated with imiquimod has been attributed to its induction of interferon (IFN)-alpha. The pr esent studies evaluated imiquimod administered orally for its ability to stimulate production of IFN and other cytokines in mice. The cytoki ne profile induced by imiquimod was compared with other known immunomo dulators. Imiquimod was found-to stimulate increased serum IFN in mice . Daily dosing of Imiquimod for five consecutive days led to diminishe d production of IFN in mice as measured after the final dose. Elevated levels of serum tumor necrosis factor (TNF)-alpha and interleukin (IL )-6 but not IL-1 alpha were found in serum from mice treated with imiq uimod. Imiquimod produced significantly higher levels of IFN but lower levels of TNF and IL-6 and IL-1 alpha than lipopolysaccharide. Polyin osinic acid:polycytidylic acid induced significantly higher amounts of IFN but lower levels of TNF and IL-6 than imiquimod. Imiquimod stimul ated significantly higher levels of IFN when compared with 2-amino-5-b romo-6-phenyl-4(3H)-pyrimidinone (ABPP) and similar levels of IFN when compared with tilorone. Neither ABPP nor tilorone induced TNF or IL-6 . Finally, imiquimod stimulated TNF, IFN, and IL-6 production in cultu res of mouse spleen and bone marrow cells. These studies demonstrate t hat imiquimod induces not only IFN but other cytokines as well, all of which may contribute to its biological activity.