Intranasal Administration of IFN-α/β Inhibits the Development of Visceral Tumor Metastases

Abstract

Intranasal administration of 10⁴ U of murine interferon (IFN)-α/β prolonged the survival time of DBA/2 mice injected i.v. with 10⁵ (>20,000 LD₅₀) IFN-α/β-resistant 3C18 Friend leukemia cells (FLC). Long-term survivors rejected a second challenge with 3C18 FLC without additional IFN-α/β treatment. IFN-α/β administered intranasally was not effective in 3C18 FLC-challenged DBA/2 mice pretreated with antibody to IFN-α/β. Recombinant human IFN-α BDBB, which is cross-reactive on mouse cells, also increased the survival time of 3C18 FLC-challenged DBA/2 mice. Placing 10⁴ U IFN-α/β twice a day into the nostrils also prolonged the survival time of DBA/2 mice with 3-day established 3C18 FLC tumors. Administration of 10⁴ U IFN-α/β into the nasopharynx was equally effective or more effective than an equivalent amount of IFN-α/β given by the i.p. or oral routes or by gavage. Intranasally administered IFN-α/β also increased the survival time of C57B1/6 mice challenged i.v. with EL4 T cell lymphoma cells, DBA/2 mice challenged i.v. with L1210R B cell lymphoma cells, and C57B1/6 (H-2^b) and DBA/2 (H-2^d) mice challenged i.v. with B16 melanoma cells (H-2^b). These results may be important in devising novel therapeutic strategies for malignant disease using type I IFN.