Abstract
Peripheral blood leukocyte cytotoxic activity was studied in cancer patients being treated with a continuous 5-day intravenous infusion of recombinant human tumor necrosis factor (TNF) at a dose of 40 µg/m2/day. All of the nine patients tested experienced a marked increase in circulating leukocyte cytotoxic activity over the 5-day course of treatment. The increase in cytotoxic activity was paralleled by an overall decrease in the number of peripheral blood leukocytes. The percentage of circulating Leu 19+ natural killer cells fell in all patients, while the numbers of both Leu 4+ T cells and Leu 19+/Leu 4+ cytotoxic T cells remained constant. Our findings suggest that the intravenous administration of recombinant TNF may be accompanied by an immunoenhancement due either to an improvement in cytotoxic cell function or to alterations in the trafficking of leukocytes.
Similar content being viewed by others
References
Sugarman BJ, Aggarwal BB, Hass PE, Figari S, Palladino MA: Recombinant human tumor necrosis factor-α: Effects on proliferation of normal and transformed cells in vitro. Science 230:943–945, 1985
Fransen L, Van Der Heyden J, Ruysschaert R, Fiers W: Recombinant tumor necrosis factor: Its effect and its synergism with interferon-γ on a variety of normal and transformed human and mouse cell lines. Eur J Cancer Clin Oncol 22:419–426, 1986
Talmadge JE, Phillips H, Schneider M, Rowe T, Pennington R, Bowersox O, Lenz B: Immunomodulatory properties of recombinant murine and human necrosis factor. Cancer Res 48:544–550, 1988
Owen-Schaub LB, Gutterman JU, Grimm EA: Synergy of tumor necrosis factor and interleukin 2 in the activation of human cytotoxic lymphocytes: Effect of tumor necrosis factor α and interleukin 2 in the generation of human lymphokine-activated killer cell cytotoxicity. Cancer Res 48:788–792, 1988
Østensen ME, Thiele DL, Lipsky PE: Tumor necrosis factor-α enhances cytolytic activity of human natural killer cells. J Immunol 138:4185–4191, 1987
Ledbetter JA, Evans RL, Lipinski M, Cunningham-Rundels C, Good RA, Herzenberg LA: Evolutionary conservation of surface molecules that distinguish T-lymphocytes helper/inducer and T-cytotoxic/suppressor subpopulations in mouse and man. J Exp Med 153:310–323, 1981
Hercend T, Griffin JD, Benussan A, Schmidt RE, Edson MA, Brennan A, Murray C, Daley JF, Schlossman SF, Ritz J: Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1 and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest 75:932–943, 1985
Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH: The relationship of CD 16 (Leu 11) and Leu 19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T-lymphocytes. J Immunol 136:4480–4486, 1986
Scuderi P, Sterling KE, Lam KS, Finley PR, Ryan KJ, Ray CG, Petersen E, Slymen DJ, Salmon SE: Raised serum levels of tumour necrosis factor in parasitic infections. Lancet 2:1364–1365, 1986
Steel RGD, Torrie JH: Principles and Procedures of Statistics: A Biomedical Approach, 2nd ed. New York, McGraw Hill, 1980
Miller RG: Simultaneous Statistical Inference, 2nd ed. New York, Springer Verlag, 1981
Haller O, Hansson M, Kiessling R, Wigzell H: Role of nonconventional natural killer cells in resistance against syngeneic tumor cells in vivo. Nature 270:609–611, 1977
Herscowitz HB, Holden HT, Bellanti JA, Ghaffar A: Manual of Macrophage Methadology. New York and Basel, Marcel Dekker, 1981
Decker T, Lohmann-Matthes ML, Gifford GE: Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated macrophages. J Immunol 138:957–962, 1987
Philip R, Epstein LB: Tumor necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, γ-interferon and interleukin-1. Nature 323:86–88, 1986
Kriegler M, Perez C, DeFay K, Albert I, Lu SD: A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: Ramifications for the complex physiology of TNF. Cell 53:45–53, 1988
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Charnetsky, P.S., Greisman, R.A., Salmon, S.E. et al. Increased peripheral blood leukocyte cytotoxic activity in cancer patients during the continuous intravenous administration of recombinant human tumor necrosis factor. J Clin Immunol 9, 34–38 (1989). https://doi.org/10.1007/BF00917125
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00917125