IFN-alpha in vivo enhances tumor necrosis factor receptor levels on hairy cells

Hairy cell leukemia (HCL) is a preplasma B cell neoplasia that is characterized by monocytopenia and responds to IFN-alpha therapy. We investigated the expression of receptors for TNF-alpha, a monocyte-derived cytokine, on the surface of hairy cells from seven HCL patients before and after treating them with IFN-alpha. Iodinated TNF-alpha binding experiments showed the presence of high affinity TNF-alpha receptors in six patients, but no specific binding was detected in the seventh. Scatchard's analysis revealed the presence of a single class of receptors, with 130 to 1200 sites/cell (mean 420) and Kd values of 0.37 to 0.89 nM. The TNF-alpha-R complex was identified by cross-linking as a single band of 94 kDa. Treatment of the patients with 3 x 10(6) U of IFN-alpha 2a markedly increased the number of TNF-alpha-R at 24 or 48 h, without changing the Kd. In the patient who lacked receptor expression on his tumor cells, high affinity TNF-alpha-R were detected at 48 h after IFN injection. These results suggest that in hairy cells, IFN-alpha can interact in vivo with TNF-alpha, through the modulation of TNF-R.