INDUCTION AND REGULATION OF IL-15 EXPRESSION IN MURINE MACROPHAGES

IL-15 is a recently described cytokine which resembles IL-2 in its bio logic activities, stimulating T cell and NK cell proliferation and act ivation as well as enhancing B cell expansion and Ab production, Unlik e IL-2, IL-15 is not produced by lymphocytes, but instead (at least am ong cells of the immune system) appears to be synthesized primarily by monocyte/macrophages. We have examined the induction of IL-15 in muri ne macrophages (by semiquantitative reverse transcriptase-PCR and bioa ssay) in response to a variety of different macrophage-activating stim uli and compared the regulation of IL-15 production to that of IL-12 a nd TNF-alpha, Optimal induction of IL-15, in each of the macrophage po pulations tested, was found to require both priming (IFN-gamma) and tr iggering (LPS, mycobacteria, or Toxoplasma gondii) stimuli. When compa red with IL-12 mRNA synthesis by the same macrophages, IL-15 mRNA prod uction was more resistant to inhibition by the down-regulatory cytokin es IL-4, IL-13, and TGF-beta. Moreover, IL-10, which is inhibitory for most other monokines, increased levels of IL-15 mRNA found after stim ulation. These data establish IL-15 as a product of the macrophage/mon ocyte lineage, which is up-regulated on activation. IL-15 could thus p lay an important role in the initiation of immune responses by microbi al agents.