Neutralizing antibodies to human interleukin 6 reverse hypercalcemia associated with a human squamous carcinoma.
Bone resorbing cytokines may be associated with abnormalities in bone cell function and calcium homeostasis in a number of pathological conditions. One of these cytokines is interleukin 6 (IL-6), which is a multifunctional cytokine which has been shown to be associated with increased formation of bone resorbing osteoclasts in vitro. In this report, we demonstrate that neutralizing antibodies to human IL-6 lower the blood calcium in nude mice carrying a human tumor associated with increased IL-6 production. There was no effect on blood calcium in hypercalcemic nude mice carrying tumors not associated with increased IL-6 production and normocalcemic tumor-bearing nude mice. These results suggest that increased production of IL-6 may contribute to disturbances in calcium homeostasis in some malignancies, and suggest that neutralization of IL-6 effects can lower the serum calcium in these tumors.
Yoneda
T
T
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877.
Nakai
M
M
Moriyama
K
K
Scott
L
L
Ida
N
N
Kunitomo
T
T
Mundy
G R
GR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D002100:Cachexia / Q000209:etiology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000209:etiology / Q000628:therapy*; D007074:Immunoglobulin G / Q000097:blood / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008297:Male; D008441:Maxillary Neoplasms / Q000097:blood* / Q000150:complications; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000032:analysis; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015850:Interleukin-6; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins