THE METABOLIC EFFECTS OF INTERLEUKIN-1-BETA ON HUMAN BONE-MARROW ADIPOCYTES

We have recently shown that interleukin 1 beta (IL-1 beta) directly re duces the number of adipocytes in cultures of human bone marrow (BM) s tromal cells. The aim of the present study was to establish the mechan isms involved in this IL-1 effect and thereby assess its importance in BM pathophysiology. Direct morphological observation showed that indi vidual adipocytes lost their fat in the presence of IL-1 beta and rega ined it when the cytokine was withdrawn. These morphological observati ons were supported by metabolic studies using [(14)]acetate as a precu rsor of storage fat. These metabolic studies showed that IL-1 beta inh ibited the incorporation of label into triglycerides. In addition, the cytokine enhanced the release of radioactivity from prelabelled adipo cytes and reduced their triglyceride stores. It was therefore conclude d that IL-1 beta can both inhibit Lipogenesis and stimulate lipolysis in BM adipocytes. Forskolin (an adenylate cyclase activator) produced lipolytic effects similar to those of IL-1 beta, while indomethacin (a n inhibitor of prostaglandin [PG] production) fully blocked the releas e of radioactivity induced by IL-1 beta and greatly increased triglyce ride synthesis. However, IL-1 beta was still able to decrease triglyce ride synthesis in the presence of indomethacin. These results indicate that a prostaglandin-dependent increase in cAMP is important in the l ipolytic effects of IL-1 beta but that the anti-lipogenic effects of t he cytokine are, at least in part, independent of PG synthesis. These observations suggest that local production of IL-1 beta has a potentia l role in regulating BM storage fat metabolism in a way that would con tribute to the energy required for the marrow's ability to expand its haematopoietic capacity.