IL-1 beta inhibits adipocyte formation in human long-term bone marrow culture

Addition of recombinant interleukin-1 beta (IL-1 beta) to human long-term bone marrow culture (LTBMC) was found to have a profound effect on adipocyte formation. Control cultures developed 133 +/- 58 adipocytes/flask compared with 3 +/- 2 adipocytes/flask in IL-1 beta-treated flasks (mean +/- SEM, n = 6 for both groups). In terms of cell number, morphology and colony forming cell, IL-1 beta did not have significant effects on LTBMC, although IL-1 beta slightly enhanced colony-stimulating activity of LTBMC-conditioned medium. To further analyze the effect of IL-1 beta on adipocytes, stromal cells were passaged to reduce hemopoietic cell content, and marrow fibroblasts were converted to adipocytes following addition of hydrocortisone. In both types of assay, IL-1 beta again reduced adipocyte formation: control 1095 +/- 76 adipocytes/flask, IL-1 beta-treated 7 +/- 2 adipocytes/flask (n = 3 for both groups). When preformed adipocytes were treated with IL-1 beta for 1 week, the number of lipid-laden cells decreased to 41 +/- 13% of its value before treatment compared to 87 +/- 9% for untreated controls. The addition of neutralizing concentrations of anti-TNF did not inhibit these effects of IL-1 beta. These results suggest that 1) adipocyte formation is not essential for healthy LTBMC growth, or at least IL-1 beta is an effective substitute for adipocytes; 2) IL-1 beta by itself does not significantly enhance hemopoiesis in LTBMC, and this has implications for clinical trials with this cytokine; 3) IL-1 beta produces major changes in stromal cell development, and 4) overgrowth of fat in marrow may reflect defective cytokine regulation in vivo.