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

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Abstract
2 Is a heterodlmerlc cytoklne that has been shown to enhance natural killer (NK) and cytotoxic T lymphocyte (CTL) responses, and to induce IFN-γ production in vitro. In this study, we have examined the effects in vivo of administering purified murine rlL-12 to normal mice. Dally injections of riL-12 I.p. (1 ng to 10 μg/day) caused dose-dependent enhancement of NK cell lytic activity in the spleens and livers of treated mice. Histologlc 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 lymphold cells from IL-12-treated mice, unlike liver and splenic lymphoid cells from control mice, spontaneously secreted IFN-γ in vitro, suggesting that they had been induced by IL-12 to produce IFN-γ in vivo. Consistent with this, IFN-γ could be detected in the serum of IL-12-treated mice. In mice which had been immunized by footpad injection of allogenelc splenocytes, dally administration of rlL-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-γ 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 tu more and infectious diseases.

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