Effects of interferon alpha on autocrine growth factor loops in B lymphoproliferative disorders

doi:10.1084/jem.172.6.1729

This Article

	Full Text (PDF, 579K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Heslop, H. E.
	Articles by Brenner, M. K.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Heslop, H. E.
	Articles by Brenner, M. K.


Social Bookmarking

	What's this?

ARTICLES

Effects of interferon alpha on autocrine growth factor loops in B lymphoproliferative disorders

HE Heslop, AC Bianchi, FT Cordingley, M Turner, W Chandima, CP De Mel, AV Hoffbrand and MK Brenner
Department of Haematology, Royal Free Hospital, London, UK.

The B lymphoproliferative disorders B chronic lymphocytic leukemia (B- CLL) and hairy cell leukemia (HCL) produce a number of autocrine growth factors, including tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-1, all of which may induce positive feedback growth loops. If such malignancies depend on these autocrine growth loops for survival, their interruption may be therapeutically valuable. Interferon alpha (IFN-alpha) abrogates TNF- or IL-6-induced proliferation of HCL and B- CLL cells in vitro and has therapeutic activity in these diseases. We have investigated the possibility that IFN-alpha may act by interrupting autocrine growth factor loops. If purified B-CLL or HCL cells are cultured in the presence of TNF, there is induction of mRNA for TNF, IL-1 alpha, IL-1 beta, and IL-6. However, culture in the presence of IFN-alpha in addition to TNF reduced the level of mRNA for all these cytokines, compared with cells cultured in TNF alone. While cytokine mRNA levels were diminished, levels of mRNA for the ribonuclease activator 2-5A synthetase were increased. Analysis of the kinetics of cytokine mRNA production showed that levels fall shortly after the rise of 2-5A synthetase mRNA. IFN-alpha may produce these effects by shortening the half-life of cytokine mRNA, since TNF mRNA half-life in B-CLL and HCL cells is substantially reduced when the cells are cultured with IFN-alpha. These data suggest that IFN-alpha may mediate its therapeutic effects in these malignancies by blocking autocrine growth factor loops.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Tilton, J. C., Johnson, A. J., Luskin, M. R., Manion, M. M., Yang, J., Adelsberger, J. W., Lempicki, R. A., Hallahan, C. W., McLaughlin, M., Mican, J. M., Metcalf, J. A., Iyasere, C., Connors, M. (2006). Diminished Production of Monocyte Proinflammatory Cytokines during Human Immunodeficiency Virus Viremia Is Mediated by Type I Interferons. J. Virol. 80: 11486-11497 [Abstract] [Full Text]
Baker, P. K., Pettitt, A. R., Slupsky, J. R., Chen, H. J., Glenn, M. A., Zuzel, M., Cawley, J. C. (2002). Response of hairy cells to IFN-alpha involves induction of apoptosis through autocrine TNF-alpha and protection by adhesion. Blood 100: 647-653 [Abstract] [Full Text]
Bernal, A., Pastore, R. D., Asgary, Z., Keller, S. A., Cesarman, E., Liou, H.-C., Schattner, E. J. (2001). Survival of leukemic B cells promoted by engagement of the antigen receptor. Blood 98: 3050-3057 [Abstract] [Full Text]
Shehata, M., Schwarzmeier, J. D., Nguyen, S. T., Hilgarth, M., Berger, R., Hubmann, R., Kickmaier, S., Decker, T. (2000). Reconstitution of Endogenous Interferon {{alpha}} by Recombinant Interferon in Hairy Cell Leukemia. Cancer Res. 60: 5420-5426 [Abstract] [Full Text]
Noraz, N., Lathey, J. L., Spector, S. A. (1997). Human Cytomegalovirus-Associated Immunosuppression Is Mediated Through Interferon-alpha. Blood 89: 2443-2452 [Abstract] [Full Text]