THE ROLE OF CYTOKINES AND HEMATOPOIETIC GROWTH-FACTORS IN THE AUTOCRINE PARACRINE REGULATION OF INDUCIBLE HEMATOPOIESIS/

To elucidate the role of hematopoietic Introduction growth factors (HG Fs) and other cytokines in the autocrine or paracrine regulation of in ducible hematopoiesis we studied cytokine gene expression in the bone marrow (BM) of patients after myelosuppressive treatment. Furthermore, we studied the cytokine gene expression profile in healthy individual s before and after bone marrow harvesting for the purpose of bone marr ow transplantation. We speculated that the bone marrow harvesting proc edure might induce changes in cytokine gene expression. No induction o f G-CSF, GM-CSF, IL-1 alpha, IL-3, IL-5, IL-8, IL-9, and IL-12 was obs erved in the BM of patients following intensive chemotherapy. Also, no up-regulation of expression of M-CSF, IL-1 beta, IL-4, IL-6, TNF-alph a, TGF-beta, IGF-1, EDF, and EPA gene was found, illustrating that the investigated cytokines probably are not relevant in the presumed auto crine/paracrine regulation of the recovery of hematopoiesis following depletion of hematopoietic progenitor cells (HPCs). Concomitantly, ele vated G-CSF plasma levels were found in these patients, suggesting tha t G-CSF has an endocrine regulatory role in inducible hematopoiesis. I nduction of GM-CSF and IL-8, but not of G-CSF or IL-3 gene expression and upregulation of IL-1 beta and IL-6 gene following BM harvesting wa s observed. This induction of GM-CSF and IL-8 may be attributed to tis sue damage rather than to HPC depletion.