Interferon-alpha (IFN-alpha) is successfully used in the therapy of hairy cell leukemia (HCL). We previously reported that IFN-alpha administered to HCL patients stimulated the levels of tumor necrosis factor (TNF) receptors on hairy cells. Here, we investigated the interactions between IFN-alpha and TNF, using the HCL cell line Eskol as a model. We showed that increased levels of TNF receptors (TNFR) induced by IFN-alpha treatment were associated with stimulation of high M(r) TNFR. Low M(r) TNFR were not detected on Eskol cells or hairy cells, either before or after IFN-alpha treatment. Furthermore, the expression of TNF mRNA increased in Eskol cells treated with IFN-alpha for 1-4 h as compared to control cells. In vivo experiments showed that IFN-alpha given to HCL patients induced both TNF mRNA expression in hairy cells and secretion of active TNF protein in patients' serum. These results provide evidence that IFN-alpha may induce an autocrine loop of TNF in HCL.
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