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(I: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(I:C)-stimulated cells led to an IL-1 release similar to that obtained with normal mice treated with silica alone. Since poly(I:C) is able to elicit the production of interferons (IFN), the involvement of IFNs was investigated in poly(I:C) activity. Neither IFN-alpha/beta nor IFN-gamma, 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-alpha/beta and IFN-gamma were unable to affect the poly(I:C) and silica induced release of IL-1. Thus, the signal provided by poly(I:C) does not appear to be mediated by IFN(s).