Macrophages From C3H/HeJ Mice Require an Additional Step To Produce Monokines: Synergistic Effects of Silica and Poly(I:C) in the Release of Interleukin 1

Resident macrophages from C3H/HeJ mice, in contrast with those of other strains of mice such as BDF1 mice, did not release a 35 kD m.w. factor having macrophage replacing activity (FRM) or interleukin 1 (IL‐1) when, respectively, cultured alone or in the presence of silica. C3H/HeJ macrophages were nevertheless capable of producing an intracellular IL‐1‐like activity. In addition, after a two‐step activation process, macrophages from BDF1 mice spontaneously released IL‐1, whereas silica was required to induce the release of IL‐1 from similarly treated C3H/HeJ macrophages. Such in vivo primed and in vitro stimulated macrophages failed to release FRM. In contrast, poly(l:C) was able to induce the release of FRM by C3H/HeJ macrophages but not that of IL‐1; moreover, the addition of silica to poly(l:C)‐stimulated cells led to an IL‐1 release similar to that obtained with normal mice treated with silica alone. Since poly(l:C) is able to elicit the production of interferons (IFN), the involvement of IFNs was investigated in poly(l:C) activity. Neither IFN‐α/β nor IFN‐γ, when used alone or in the presence of silica, could induce the release of IL‐1 by C3H/HeJ macrophages. In addition, antibodies to IFN‐α/β and IFN‐γ were unable to affect the poly(l:C) and silica induced release of IL‐1. Thus, the signal provided by poly(l:C) does not appear to be mediated by IFN(s).