It is well known that bacterial lipopolysaccharide (LPS) induces the synthesis of tumor necrosis factor α (TNF-α) and other inflammatory cytokines by primary monocytes and macrophages and that the Th1 lymphokines, interleukin-2 (IL-2) and interferon-γ (IFN-γ) augment this response. We investigated the ability of IL-2 and IFN-γ to induce the production of TNF-α mRNA and protein independently of LPS and the modulation of this response by macrophage colony-stimulating factor (M-CSF) and IL-10. We found that IL-2 and IFN-γ were both able to induce the accumulation of TNF-α mRNA, albeit with slower kinetics than LPS, and that they acted synergistically. However, very little TNF bioactivity was secreted by lymphokine-stimulated macrophages unless LPS was also added. This finding underscores the importance of translational effects in the control of TNF production. M-CSF and IL-10 strongly inhibited TNF production at the level of both mRNA and bioactivity but had no effect on the production of IL-6. Bone marrow-derived or thiogycollate-elicited macrophages from the NZW mouse strain, which have been reported to be deficient in their ability to produce TNF, were at least as responsive to LPS or lymphokines as those taken from the C57BI/6 strain and were similarly affected by M-CSF and IL-10. Therefore, the genetic defect of NZW mice is not a primary deficiency in TNF production.
- Macrophage colony-stimulating factor
- Translational regulation
ASJC Scopus subject areas
- Cell Biology