Tumor necrosis factor-beta 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-beta (TNF-beta), 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-beta detected elevated TNF-beta in the sera of ATL patients with hypercalcemia. Immunostaining by monoclonal anti-TNF-beta antibody demonstrated the presence of TNF-beta in both HTLV-I infected cell lines and freshly isolated ATL cells. Furthermore biological TNF-beta activity assay including inhibition of anti-TNF-beta antibody confirmed the conventional documentation of TNF-beta activity in the sera and culture supernatants of HTLV-I infected cell lines. These studies showed that the TNF-beta 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).
Ishibashi
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
Kodama
M
M
Hanada
S
S
Arima
T
T
D000818:Animals; D016723:Bone Remodeling; D001862:Bone Resorption / Q000209:etiology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology*; D015458:Leukemia, T-Cell / Q000150:complications; D008233:Lymphotoxin-alpha / Q000032:analysis / Q000502:physiology*; D009101:Multiple Myeloma / Q000150:complications
D016207:Cytokines; D008233:Lymphotoxin-alpha