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The effects of indomethacin and interleukin-2 on the proliferation of lymphocytes from patients with lung cancer

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Abstract

The effects of the addition of indomethacin and interleukin-2 (IL-2) to phytohemagglutinin (PHA)-stimulated lymphocytes from patients with untreated squamous-cell carcinoma of the lung and with chronic obstructive pulmonary disease and from normal individuals were studied. In 13 of 21 patients with lung carcinoma, the response of lymphocytes to PHA stimulation was significantly augmented by indomethacin. In these 13 patients, the nonaugmented PHA response was also significantly depressed, with only 1 patient falling in the normal range. In the other 8 patients, the average PHA reactivity was normal, as was the degree of augmentation by indomethacin. In additional studies, IL-2 was added to PHA-stimulated lymphocytes with and without the addition of indomethacin. In the normal group, IL-2 further increased PHA reactivity by an average of 46.0%. The addition of indomethacin to these cultures increased the PHA reactivity by only 8.8%, which is similar to the indomethacin effect for the PHA-stimulated cells without the addition of IL-2. In the cancer group, the PHA reactivity of 13 of 19 patients was significantly increased by the addition of IL-2. When indomethacin was added simultaneously with IL-2, the proliferative response for 12 of 19 patients was increased significantly more than for the normal controls. Thus, this study indicates that the PHA reactivity of lymphocytes from many lung carcinoma patients is augmented to a greater extent than for normal individuals by inhibiting prostaglandin synthesis. Also, the addition of IL-2 to these PHA-stimulated cultures did not mimic the addition of indomethacin, but instead the effects were usually additive. These findings may have clinical implications with regard to designing new clinical trials in patients with lung carcinoma.

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References

  1. Golub SH, O'Connell TX, Morton DL: Correlation in in vivo and in vitro assays of immunocompetence in cancer patients. Cancer Res 34:1833–1837, 1974

    Google Scholar 

  2. Holmes EC, Golub SH: Immunologic defects in lung cancer patients. J Thor Card Surg 71:161–167, 1976

    Google Scholar 

  3. Stefani S, Kerman R, Abbate J: Immune evaluation of lung cancer patients undergoing radiation therapy. Cancer 37:2792–2796, 1976

    Google Scholar 

  4. Jerrells TR, Dean JH, Herberman RB: Relationship between T-lymphocyte levels and lymphoproliferative responses to mitogens and alloantigens in lung and breast cancer patients. Int J Cancer 21:282–290, 1978

    Google Scholar 

  5. Potvin C, Dellon AL, Chretien PB: T-cell levels in bronchogenic carcinoma—Correlations with tumor stage and clinical course. Surg For 25:96–97, 1974

    Google Scholar 

  6. Brugarolas A, Han T, Takita H, Minowada J: Immunologic assays in lung cancer: Skin tests, lymphocyte blastogenesis and rosette-forming cell count. NY State J Med 73:747–750, 1973

    Google Scholar 

  7. Golub SH, Holmes EC: In vitro assays of immunocompetence in patients with lung cancer treated with levamisole. Cancer Immunol Immunother 7:143–149, 1979

    Google Scholar 

  8. Han T: Impaired lymphocyte responses to allogeneic cultured lymphoid cells in patients with lung cancer. N Engl J Med 286:605–606, 1972

    Google Scholar 

  9. Han T, Takita H: Immunologic impairment in bronchogenic carcinoma: A study of lymphocyte response to phytohemagglutinin. Cancer 30:616–620, 1972

    Google Scholar 

  10. Kerman RH, Stefani St S: Phytohemagglutinin stimulation of lymphocytes in lung cancer patients. Oncology 34:10–12, 1977

    Google Scholar 

  11. Reese JC, Rossio JL, Wilson HE, Minto JP, Dodd MC: Cellular immunity in neoplasia: Antigen and mitogen responses in patients with bronchogenic carcinoma. Cancer 36:2010–2015, 1975

    Google Scholar 

  12. Giuliano AE, Rangel D, Golub SH, Holmes EC, Morton DL: Serum-mediated immunosuppression in lung cancer. Cancer 43:917–924, 1979

    Google Scholar 

  13. Sample WF, Gartner HR Jr, Chretien RB: Inhibition of phytohemagglutinin induced in vitro lymphocyte transformation by serum from patients with carcinoma. J Natl Cancer Inst 46:1291–1297, 1971

    Google Scholar 

  14. Ruscetti FW, Gallo RC: Human T-lymphocyte growth factor: Regulation of growth and function of T-lymphocytes. Blood 57:379–399, 1981

    Google Scholar 

  15. Smith KA, Ruscetti FW: T-cell growth factor and the culture of cloned functional T-cells. Adv Immunol 31:137–175, 1981

    Google Scholar 

  16. Goodwin JS, Messner RP, Bankhurst AD,et al. Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med 297:963–968, 1977

    Google Scholar 

  17. Han T, Takita H: Indomethacin-mediated enhancement of lymphocyte response to mitogens in healthy subjects and lung cancer patients. Cancer 46:2416–2420, 1980

    Google Scholar 

  18. Maca RD, Panje WR: Indomethacin sensitive suppressor cell activity in head and neck cancer patients pre- and postirradiation therapy. Cancer 50:483–489, 1982

    Google Scholar 

  19. Vosixa G, Thies J: Effect of indomethacin on blastogenesis of lymphocytes from cancer patients: Differentiation of patient types. Clin Immunol Immunopathol 13:30–38, 1979

    Google Scholar 

  20. Maca RD, Bonnard GD, Herberman RB: The suppression of mitogen-and alloantigen-stimulated peripheral blood lymphocytes by cultured human T-lymphocytes. J Immunol 123:246–251, 1979

    Google Scholar 

  21. Baker PE, Fahey JV, Munck A: Prostaglandin inhibition of T-cell proliferation is mediated at two levels. Cell Immunol 61:52–61, 1981

    Google Scholar 

  22. Rappaport RS, Dodge GR: Prostaglandin E inhibits the production of human interleukin-2. J Exp Med 155:943–948, 1982

    Google Scholar 

  23. Tilden AB, Balch CM: A comparison of PGE2 effects on human suppressor cell function and on interleukin-2 function. J Immunol 129:2469–2473, 1982

    Google Scholar 

  24. Webb DR, Nowowiejski I: Mitogen-induced changes in lymphocyte prostaglandin levels: A signal for the induction of suppressor cell activity. Cell Immunol 41:72–85, 1978

    Google Scholar 

  25. Rogers TJ, Nowowiejski I, Webb DR: Partial characterization of a prostaglandin-induced suppressor factor. Cell Immunol 50:82–93, 1980

    Google Scholar 

  26. Goodwin JS, Bankhurst AD, Messner RP: Suppression of human T-cell mitogenesis by prostaglandin. J Exp Med 146:1719–1733, 1977

    Google Scholar 

  27. Stobo JD, Kennedy MS, Goldyne ME: Prostaglandin E modulation of the mitogenic response of human T-cells. J Clin Invest 64:1188–1195, 1979

    Google Scholar 

  28. Tomar RH, Darrow TL, John PA: Response to and production of prostaglandin by murine thymus, spleen, bone marrow, and lymph node cells. Cell Immunol 60:335–646, 1981

    Google Scholar 

  29. Bray MA, Gordon D, Morley J: Regulation of lymphokine secretion by prostaglandins. Agents Actions 6:171–175, 1976

    Google Scholar 

  30. Brunda MJ, Herberman RB, Holden HT: Inhibition of murine natural killer cell activity by prostaglandins. J Immunol 124:2682–2687, 1980

    Google Scholar 

  31. Droller MJ, Schneider MU, Perlmann P: A possible role of prostaglandins in the inhibition of natural and antibody dependent cell mediated cytotoxicity against tumor cells. Cell Immunol 39:165–177, 1978

    Google Scholar 

  32. Wolf M, Droege W: Inhibition of cytotoxic responses by prostaglandin E2 in the presence of interleukin-2. Cell Immunol 72:286–293, 1982

    Google Scholar 

  33. Schultz RM, Pavlidis NA, Stylos WA, Chirigos MA: Regulation of macrophage tumoricidal function: A role for prostaglandins of the E-series. Science 202:320–321, 1978

    Google Scholar 

  34. Goodwin JS, Bankhurst AD, Murphy SA,et al. Partial reversal of the cellular immune defect in common variable immunodeficiency with indomethacin. J Clin Lab Immunol 1:197–199, 1978

    Google Scholar 

  35. Panje WR: Regression of head and neck carcinoma with a prostaglandin-synthesis inhibitor. Arch Otolaryngol 107:658–663, 1981

    Google Scholar 

  36. Bennet A, Houghton J, Leaper DJ, Stamford IF: Cancer growth, response to treatment and survival time in mice: Beneficial effect of the prostaglandin synthesis inhibitor flurbiprofen. Prostaglandins 17:179–189, 1979

    Google Scholar 

  37. Hial V, Horakova Z, Shaff RE, Beaven MA: Alteration of tumor growth by aspirin and indomethacin: Studies with two transplantable tumors in mouse. Eur J Pharmacol 37:367–376, 1976

    Google Scholar 

  38. Trevisani A, Ferretti E, Capuzzo A, Tomasi V: Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumor growth by nonsteroidal anti-inflammatory drugs. Br J Cancer 41:341–347, 1980

    Google Scholar 

  39. Lynch NR, Salomon J: Tumor growth inhibition and potentiation of immunotherapy by indomethacin in mice. J Natl Cancer Inst 62:117–121, 1979

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Veterans Administration Medical Center and Louisiana State University Medical School—Shreveport, 71130, Shreveport, Louisiana

    Richard D. Maca, John G. Burford & Ronald T. Taylor

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  1. Richard D. Maca
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  2. John G. Burford
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  3. Ronald T. Taylor
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Maca, R.D., Burford, J.G. & Taylor, R.T. The effects of indomethacin and interleukin-2 on the proliferation of lymphocytes from patients with lung cancer. J Clin Immunol 5, 158–165 (1985). https://doi.org/10.1007/BF00915506

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