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Individual and Combined Tumoricidal Effects of Dexamethasone and Interferons On Human Leukocyte Cell Lines¹

Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756

We investigated the influence of glucocorticoids on two effects of interferons (IFNs) which are thought to relate to their antitumor actions: cytotoxic activity and induction of HLA antigen expression. We treated human myeloid cell lines (U-937, HL-60, THP-1, K-562, and KG-1a), and T- (MOLT-4) and B- (Dandi) lymphoblastic cell lines with concentrations of IFN-, IFN-, and dexamethasone (Dex) which are commonly achieved in the circulation following therapeutic administration. The results show that for every cell line except Daudi, the greatest inhibition of cell growth occurred when IFN- and Dex treatments were combined. The advantage of combined IFN- and Dex treatment over treatment with either agent alone was most dramatic for the three cell lines (U-937, HL-60, and THP-1) which have monocytoid characteristics. There was also more growth inhibition by the combination of IFN- and Dex than by either agent alone for all seven cell lines tested. The induction of HLA antigen expression by IFN- and IFN-, an effect which could increase recognition of the tumor cells by the immune system, was as great or greater in the presence of Dex as in its absence. These results demonstrate that glucocorticoids do not inhibit, and in some cases enhance, two effects of IFNs that appear to be related to their antitumor actions: inhibition of tumor cell proliferation and enhancement of HLA antigen expression.

¹ This research is supported by NIH Grants CA 17323 and AM 33100. The flow cytometer is a gift of the Fannie E. Rippel Foundation, and is supported in part by the Core Grant of the Norris Cotton Cancer Center (CA 23108).

² Supported by a graduate fellowship from the Cancer Research Institute.

³ Partially supported by Junior Faculty Research Award 110 from the American Cancer Society. To whom requests for reprints should be addressed.

Received 4/15/87. Revised 9/29/87. Accepted 11/ 4/87.

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