This Article Full Text 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 Shehata, M. Articles by Decker, T. Search for Related Content PubMed PubMed Citation Articles by Shehata, M. Articles by Decker, T.

Reconstitution of Endogenous Interferon by Recombinant Interferon in Hairy Cell Leukemia¹

University of Vienna, Clinic of Internal Medicine I, Department of Hematology, [M. S., J. D. S., M. H.], and L. Boltzmann Institute for Cytokine Research [M. S., J. D. S., S. T. N., R. B., R. H., S. K.], University of Vienna, A-1090 Vienna, Austria, and Institute for Microbiology and Genetics, A-1030 Vienna, Austria [T. D.]

Recombinant human IFN (rhIFN-) plays an important role in the treatment of hairy cell leukemia (HCL). However, the mechanisms leading to its beneficial effect are not completely clarified, and there is no information on IFN- gene expression in this disease. Therefore, we investigated the pattern of IFN- gene expression and protein production in HCL and their potential regulation by rhIFN-. Blood samples from 10 patients with HCL and 8 healthy donors (HD) were investigated. Expression of IFN- mRNA was assessed by reverse transcription-PCR analysis in peripheral blood mononuclear cells (PBMCs) under basal conditions and on induction with rhIFN- and polyionosinic-polycytidylic acid [poly(I·C)]. IFN- concentrations in plasma and culture supernatants were measured by immunoassays, and intracellular IFN- was evaluated by fluorescence-activated cell sorting analysis. Results showed that, in contrast to blood samples from HDs, freshly isolated PBMCs from untreated HCL patients did not express IFN- mRNA, whereas IFN- transcripts were found in patients who were under rhIFN- therapy. Plasma of untreated patients contained no, or extremely low levels of, IFN- as compared with plasma of treated patients and HDs. Ex vivo treatment of PBMCs with rhIFN- or poly(I·C) resulted in a remarkable up-regulation of IFN- at the mRNA and protein level. In HCL, however, the amounts of IFN- protein remained less than in HD. Inhibition of IFN- transcription was found after exposure of PBMCs to serum from untreated patients. Finally, a reduced capacity to produce IFN- was found within B- cell, T-cell, and monocyte compartments in HCL patients, which could be enhanced by rhIFN-. The results demonstrate the ability of rhIFN- to up-regulate the expression of IFN- gene and protein production and suggest that priming the production of endogenous IFN- is a critical step in the mechanism of action of rhIFN- in HCL.

This article has been cited by other articles:

				V. Vanhentenrijk, C. De Wolf-Peeters, and I. Wlodarska Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature Blood, July 1, 2004; 104(1): 250 - 255. [Abstract] [Full Text] [PDF]