Administration of recombinant IL-12 to normal mice enhances cytolytic lymphocyte activity and induces production of IFN-gamma in vivo

• Published in: International immunology Vol. 6; no. 1; p. 157
• Main Authors: Gately, M K, Warrier, R R, Honasoge, S, Carvajal, D M, Faherty, D A, Connaughton, S E, Anderson, T D, Sarmiento, U, Hubbard, B R, Murphy, M
• Format: Journal Article
• Language: English
• Published: England 01.01.1994
• Subjects: Animals; Cytotoxicity Tests, Immunologic; Immunophenotyping; Interferon-gamma - biosynthesis; Interferon-gamma - drug effects; Interleukin-12; Interleukins - pharmacology; Killer Cells, Natural - drug effects; Liver - drug effects; Lung - drug effects; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Recombinant Proteins - pharmacology; Spleen - drug effects; T-Lymphocytes, Cytotoxic - drug effects; Tumor Cells, Cultured
• ISSN: 0953-8178
• DOI: 10.1093/intimm/6.1.157

IL-12 is a heterodimeric cytokine that has been shown to enhance natural killer (NK) and cytotoxic T lymphocyte (CTL) responses, and to induce IFN-gamma production in vitro. In this study, we have examined the effects in vivo of administering purified murine rIL-12 to normal mice. Daily injections of rIL-12 i.p. (1 ng to 10 micrograms/day) caused dose-dependent enhancement of NK cell lytic activity in the spleens and livers of treated mice. Histologic examination of the livers of IL-12-treated mice revealed focal mononuclear cell infiltrates, and flow cytometry studies indicated that the livers of IL-12-treated mice contained increased numbers of NK cells, CD8+ T cells, and monocytes. Liver and splenic lymphoid cells from IL-12-treated mice, unlike liver and splenic lymphoid cells from control mice, spontaneously secreted IFN-gamma in vitro, suggesting that they had been induced by IL-12 to produce IFN-gamma in vivo. Consistent with this, IFN-gamma could be detected in the serum of IL-12-treated mice. In mice which had been immunized by footpad injection of allogeneic splenocytes, daily administration of rIL-12 i.p. was shown to enhance the specific CTL response in the draining lymph nodes. Thus, these studies demonstrate that IL-12 can enhance NK and CTL activity and induce IFN-gamma production in vivo, as well as in vitro, and suggest possible mechanisms by which IL-12 may exert therapeutic effects in the treatment of some tumors and infectious diseases.