Tumor Necrosis Factor-β and Hypercalcemia

Hypercalcemia in hematological malignancy is frequently encountered in lymphoid malignancies such as adult T-cell leukemia (ATL) and multiple myeloma and is difficult to manage. As a causative agent of hypercalcemia in ATL, tumor necrosis factor-β (TNF-β), previously known as lymphotoxin, has been carefully studied and reviewed here. Bone resorption studies showed the presence of activity in culture supernatants of HTLV-I infected cells. Enzyme linked immunosorbent assays (ELISA) for TNF-β detected elevated TNF-β in the sera of ATL patients with hypercalcemia. Immunostaining by monoclonal anti-TNF-β antibody demonstrated the presence of TNF-β in both HTLV-I infected cell lines and freshly isolated ATL cells. Furthermore biological TNF-β activity assay including inhibition of anti-TNF-β antibody confirmed the conventional documentation of TNF-β activity in the sera and culture supernatants of HTLV-I infected cell lines. These studies showed that the TNF-β secreted from ATL cells might be one of the factors contributing to the hypercalcemia in patients with ATL functioning as an osteoclast activating factor (OAF).