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Immunomodulatory Properties of Recombinant Murine and Human Tumor Necrosis Factor¹

Preclinical Screening Laboratory, National Cancer Institute-Frederick Cancer Research FAcility, Frederick, Maryland 21701

Tumor necrosis factor has traditionally been thought to have direct cytostatic and cytotoxic properties with little or no direct immunomodulatory activity. We report here that tumor necrosis factor is able to activate macrophages both in vitro and in vivo and can increase a mixed lymphocyte response and act as an adjuvant for both T- and B-cells in vivo. Adjuvant activity in T-cells occurred in conjunction with the administration of a suboptimal syngeneic tumor cell vaccine. In addition, tumor necrosis factor demonstrated a potent dose-dependent effect on bone marrow stem cell number, dramatically depressing cellularity and thus total stem cell number. An appreciable interval is required for recovery from such stem cell depletion. Therefore, the study of the therapeutic activity of tumor necrosis factor must include a consideration of its immunomodulatory properties.

¹ This research was sponsored by the Biological Resources Branch, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, Department of Health and Human Services, under Contract N01-23910 with Program Resources, Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.

² To whom requests for reprints should be addressed. Present address: Smith, Kline, and French Laboratories, Research and Development, P. O. Box 1539, L-101, King of Prussia, PA 19406-0939.

Received 3/24/87. Revised 8/ 5/87. Revised 10/16/87. Accepted 10/19/87.

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