IL-1-BETA INHIBITS ADIPOCYTE FORMATION IN HUMAN LONG-TERM BONE-MARROWCULTURE

Addition of recombinant interleukin-1beta (IL-1beta) to human long-ten n bone marrow culture (LTBMC) was found to have a profound effect on a dipocyte formation. Control cultures developed 133 +/- 58 adipocytes/f lask compared with 3 +/- 2 adipocytes/flask in IL-1beta-treated flasks (mean +/- SEM, n=6 for both groups). In terms of cell number, morphol ogy and colony forming cell, IL-1beta did not have significant effects on LTBMC, although IL-1beta slightly enhanced colony-stimulating acti vity of LTBMC-conditioned medium. To further analyze the effect of IL- 1beta on adipocytes, stromal cells were passaged to reduce hemopoietic cell content, and marrow fibroblasts were converted to adipocytes fol lowing addition of hydrocortisone. In both types of assay, IL-1beta ag ain reduced adipocyte formation: control 1095 +/- 76 adipocytes/flask, IL-1beta-treated 7 +/- 2 adipocytes/flask (n=3 for both groups). When preformed adipocytes were treated with IL-1beta for 1 week, the numbe r of lipid-laden cells decreased to 41 +/- 13% of its value before tre atment compared to 87 +/- 9% for untreated controls. The addition of n eutralizing concentrations of anti-TNF did not inhibit these effects o f IL-1beta. These results suggest that 1) adipocyte formation is not e ssential for healthy LTBMC growth, or at least IL-1beta is an effectiv e substitute for adipocytes; 2) IL-1beta by itself does not significan tly enhance hemopoiesis in LTBMC, and this has implications for clinic al trials with this cytokine; 3) IL-1beta produces major changes in st romal cell development, and 4) overgrowth of fat in marrow may reflect defective cytokine regulation in vivo.