Interleukin-4 regulates mRNA accumulation of macrophage-colony stimulating factor by fibroblasts: synergism with interleukin-1β

Summary. We demonstrate that macrophage-colony stimulating factor (M-CSF) is expressed in human fibroblasts at the mRNA and protein level. Following activation with both interleukin (IL)-1β and IL-4. fibroblasts synthesized M-CSF transcripts detectable by Northern blot analysis with peak expression occurring at 8 h and 12 h, respectively. Exposure of fibroblasts to both cytokines resulted in M-CSF protein release at 60 h of c. 500 U/ml (for IL-1β) and 1000 U/ml (for IL-4), relative to a control preparation of recombinant human M-CSF in a murine bone marrow colony assay. Both interleukins synergized to enhance M-CSF mRNA accumulation and their ability to induce M-CSF transcripts could be abolished by treatment with specific neutralizing antibodies. These observations provide support for the idea that fibroblasts may control monocyte/macrophage development and function, and that IL-1β and IL-4 are involved in the regulation of this process.