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Lymphokine-induced Monocytic Differentiation as a Possible Mechanism for Hypercalcemia Associated with Adult T-Cell Lymphoma

Departments of Medicine, Microbiology and Immunology, University of North Carolina Medical School, Chapel Hill, North Carolina 27514 [R. C. D., S. L. N., M. S. C., T. K. G.], Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland [C. F. W.]; and Department of Medicine, University of Colorado, Denver, Colorado [P. A. B.]

Patients with adult T-cell lymphoma frequently have hypercalcemia. Bone biopsies from these patients show increased numbers of osteoclasts. We hypothesized that substances produced by the malignant T-cell caused these phenomena by increasing the formation and/or activity of osteoclasts. To test this hypothesis, we cultured U937 cells in conditioned media from a clonal T-cell line derived from a patient with adult T-cell lymphoma and hypercalcemia. This conditioned media produced maturational changes in the U937 cells as evidenced by decreased proliferation, increased adherence, increased expression of complement receptors, and formation of multinucleated giant cells. These changes were synergistically enhanced by the addition of 1,25-dihydroxyvitamin D₃ which is known to promote monocyte differentiation. We also tested interleukin 2 and - and -interferon to see if they were responsible for the maturational changes. Although some effects were seen, these lympokines could not account for all the changes induced by the T-cell conditioned media. These findings support the above hypothesis and suggest that other unidentified factors may promote the differentiation of osteoclast precursors and be involved in the pathogenesis of the hypercalcemia.

¹ Recipient of Grant AM-07129 from NIH and Grant IN-15-Y from the American Cancer Society. To whom requests for reprints should be addressed, at Department of Medicine, Division of Endocrinology, 521 Clinical Sciences Bldg. 229H, University of North Carolina School of Medicine, Chapel Hill, NC 27514.

² Recipient of an Investigator Award from the National Arthritis Foundation.

³ Recipient of Grant HD-13547 from NIH.

Received 8/13/84. Revised 1/22/85. Accepted 2/28/85.

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