CHRONIC ADMINISTRATION OF TRANSFORMING GROWTH-FACTOR-BETA SUPPRESSES ERYTHROPOIETIN-DEPENDENT ERYTHROPOIESIS AND INDUCES TUMOR-NECROSIS-FACTOR IN-VIVO

Transforming growth factor beta is a known inhibitor of the proliferation and differentiation of early haematopoietic progenitors but has no effect on mature erythroid cells in vitro. Mice injected with rhTGFbeta1 exhibited severe and progressive suppression of erythropoiesis manifested by a decline of reticulocyte count, marrow erythroblasts and marrow and spleen CFU-E, which could be prevented by administration of erythropoietin. This suppression of erythropoiesis was associated with the appearance of tumour necrosis factor in the blood, development of pronounced cachexia and depression of serum erythropoietin levels. TGFbeta induces TNF in vivo that leads to cachexia, decrease of serum erythropoietin levels and suppression of erythropoietin dependent erythropoiesis.