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Neutralizing Antibodies to Human Interleukin 6 Reverse Hypercalcemia Associated with a Human Squamous Carcinoma¹

Division of Endocrinology and Metabolism, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7877 [T. Y., M. N., K. M., L. S., G. R. M.], and Medical Devices and Diagnostic Research Laboratories, Toray Industries, Inc., IIII Tebiro, Kamakura, Kanagawa 248, Japan [N. I., T. K.]

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.

¹ This work was supported in part by Grants CA-4035, AR-28149, AR-39529, and DE-08569.

² To whom requests for reprints should be addressed, at The University of Texas Health Science Center at San Antonio, Division of Endocrinology and Metabolism, Department of Medicine, 7703 Floyd Curl Drive, San Antonio, TX 78284-7877.

Received 12/ 3/92. Accepted 12/31/92.

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