Mucosal cytokine therapy: marked antiviral and antitumor activity

• Published in: Journal of interferon & cytokine research Vol. 19; no. 8; p. 911
• Main Authors: Tovey, M G, Meritet, J F, Guymarho, J, Maury, C
• Format: Journal Article
• Language: English
• Published: United States 01-08-1999
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Antiviral Agents - therapeutic use; Friend murine leukemia virus - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Humans; Interferons - therapeutic use; Interleukins - therapeutic use; Lethal Dose 50; Leukemia, Experimental - drug therapy; Leukemia, Experimental - pathology; Mice; Mucous Membrane - drug effects; Neoplasm Transplantation; Recombinant Proteins - therapeutic use; Survival Rate; Virus Diseases - drug therapy; Virus Replication - drug effects
• ISSN: 1079-9907
• DOI: 10.1089/107999099313451

Mucosal administration of the Th1 stimulatory cytokines interleukin-2 (IL-2), IL-12, IL-15, IL-18, or granulocyte-macrophage colony-stimulating factor (GM-CSF) induced antiviral activity in mice challenged systemically with a lethal dose of encephalomyocarditis virus (EMCV) similar to that observed following parenteral administration. In contrast, mucosal administration of the Th2 stimulatory cytokines IL-4, IL-5, IL-10, or IL-13 did not affect significantly the survival of EMCV-infected animals. Mucosal administration of IL-2 or IL-12 also exerted a marked antitumor activity in mice inoculated intravenously with Friend erythroleukemia cells. Recombinant IL-2 and IL-18, but none of the other recombinant cytokines tested, induced low levels of IFN in vitro. Polyclonal antibodies to both mouse and human interferon-alpha/beta (IFN-alpha/beta) abrogated the antiviral activity of IL-2 in vivo, even though the anti-human IFN-alpha/beta antibody did not neutralize mouse IFN-alpha/beta, and neither antibody bound to IL-2. IL-15 did not exhibit antiviral activity in IFN-alpha/beta R-/- mice, which are deficient in natural killer (NK) cell activity. These results suggest that mucosal Th1 cytokine therapy induces a soluble factor or activates a specific cell population in the lymphoid or epithelial tissue of the oropharyngeal cavity, which potentiates elimination of virus-infected or neoplasic cells systemically.