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Interleukin 6 Reduces Lipoprotein Lipase Activity in Adipose Tissue of Mice in Vivo and in 3T3-L1 Adipocytes: A Possible Role for Interleukin 6 in Cancer Cachexia

Laboratory of Cellular and Developmental Biology, National Institute of Diabetes, Digestive and Kidney Disease [A. S. G., R. O. S.]; Laboratory of Genetics [R. P. N.] and Surgery Branch [J. M., D. J.], National Cancer Institute; and Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Development [J. C. C.], NIH, Bethesda, Maryland 20892

To investigate whether interleukin 6 (IL-6) might be a potential mediator of the depleted fat reserves observed in malignancy-associated cachexia, we measured lipoprotein lipase (LPL) activity in adipose tissue of mice after administration of IL-6 or tumor necrosis factor and in cultured adipocytes after addition of these cytokines. Injection of IL-6 i.p. reduced adipose tissue LPL activity by 53% within 4.5 to 5.5 h. Injection of tumor necrosis factor elevated serum IL-6 levels and reduced adipose tissue LPL activity by 70%. Both human and murine IL-6 reduced heparin-releasable LPL activity in 3T3-L1 adipocytes in a dose-dependent manner; half-maximal inhibition of LPL activity was achieved with 5000 hybridoma growth factor units/ml. Thus, IL-6 reduces adipose LPL activity and may contribute to the loss of body fat stores associated with some cases of cancer cachexia. Since tumor necrosis factor increases circulating IL-6, some of its effects may be mediated or potentiated by IL-6.

¹ To whom requests for reprints should be addressed, at LCDB, NIH, Building 6, Rm. B1-13, Bethesda, MD 20892.

² Work done in partial fulfillment of Ph.D. requirements, Dept. of Genetics, George Washington University, Washington, DC.

Received 1/14/92. Accepted 5/12/92.

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