This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brach, M. A. Articles by Herrmann, F. Search for Related Content PubMed PubMed Citation Articles by Brach, M. A. Articles by Herrmann, F.

Synergy of Interleukin 3 and Tumor Necrosis Factor in Stimulating Clonal Growth of Acute Myelogenous Leukemia Blasts Is the Result of Induction of Secondary Hematopoietic Cytokines by Tumor Necrosis Factor ¹

Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg [M. A. B., H-J. G., Y. A., S. d. V., R. M., F. H.], and Department of Hematology and Oncology, Free University of Berlin, Berlin [W-D. L.], Federal Republic of Germany

Colony growth of leukemic colony-forming units (L-CFU) obtained from patients with primary acute myelogenous leukemia stimulated with recombinant human interleukin 3 (rh IL-3) is significantly potentiated when recombinant human tumor necrosis factor (rh TNF-) is present in cultures. The costimulatory activity of tumor necrosis factor (TNF) is dose dependent and maximum at TNF- concentrations of 10 ng/ml. At high density, L-CFU proliferatively respond to TNF- stimulation in the absence of exogenous rh IL-3. Studies of the mechanism of action of rh TNF- on acute myelogenous leukemia L-CFU growth suggest that TNF- acts by inducing release of growth stimulatory hematopoietic cytokines by the leukemic cells themselves, including IL-1, IL-1ß, Granulocyte-macrophage colony-stimulating factor (CSF), granulocyte CSF, and IL-6. Treatment of L-CFU cultures, with neutralizing antibodies to IL-1, IL-1ß, granulocyte-macrophage CSF, granulocyte CSF, and IL-6 to eliminate the endogenous source of these factors is associated with significant inhibition of the synergistic interplay of TNF- and IL-3.

¹ Supported by the Mildred Scheel Stiftung (to M. A. B. and F. H.) and the Alexander von Humboldt Stiftung (to Y. A.).

² To whom requests for reprints should be addressed, at Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Str. 55, D-7800 Freiburg i.Br., FRG.

Received 5/30/91. Accepted 2/ 7/92.

This article has been cited by other articles:

				C. Garcia-Ruiz, A. Colell, M. Mari, A. Morales, and J. C. Fernandez-Checa Direct Effect of Ceramide on the Mitochondrial Electron Transport Chain Leads to Generation of Reactive Oxygen Species. ROLE OF MITOCHONDRIAL GLUTATHIONE J. Biol. Chem., April 25, 1997; 272(17): 11369 - 11377. [Abstract] [Full Text] [PDF]

				F Santiago-Schwarz, J Tucci, and S. Carsons Endogenously produced interleukin 6 is an accessory cytokine for dendritic cell hematopoiesis Stem Cells, March 1, 1996; 14(2): 225 - 231. [Abstract]