Immunological effects of levamisole in vitro

J. H. Schiller, M. Lindstrom, P. L. Witt, J. A. Hank, D. Mahvi, R. J. Wagner, P. Sondel, E. C. Borden

Research output: Contribution to journalArticle

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Abstract

Levamisole, an antihelminthic drug with immunological properties, has recently been reported to have antitumor activity when administered with 5-fluorouracil in patients with Duke's C colorectal carcinoma. The mechanism of this antitumor effect is unknown, but has been postulated to be related to levamisole's immunomodulatory properties. To define further the immunomodulatory activities of levamisole, we studied the in vitro effects of levamisole on monocyte and lymphocyte cytotoxicity, activation, and proliferation; induction of cytokine-induced proteins; and expression of tumor-associated antigens. Experiments utilized peripheral blood mononuclear cells from normal donors incubated in the presence of increasing concentrations of levamisole (0.1 to 100 μg/ml). Levamisole had no consistent effect on induction of 2',5'-oligoadenylate synthetase activity or indoleamine-2,3-dioxygenase activity, or production of tumor necrosis factor. Levamisole had no effect on monocyte cytotoxicity or expression of HLA-DR, HLA-DQ, HLA-DP, and the Fc receptor. Similarly, levamisole had no significant effect on NK or LAK cytotoxicity or the immunological activation of T-lymphocytes, assessed by expression of CD3, CD4, CD8, CD16, CD25, and CD56. Proliferation of lymphocytes from normal donors, patients with benign polyps, and patients with malignancies, with or without IL-2 or irradiated LS174T cells, was not significantly increased overall. No significant enhancement in the expression of three tumor-associated antigens (880364, NRCO-4, and ING-1) and the intercellular adhesion molecule-1 (ICAM-1) antigen on four human cancer cell lines was observed following in vitro exposure to levamisole. We conclude that levamisole is not a potent modulator of the immune parameters we examined, and that the mechanism behind the unique clinical interaction between levamisole and 5-fluorouracil in colorectal carcinoma remains to be identified.

Original languageEnglish (US)
Pages (from-to)297-306
Number of pages10
JournalJournal of Immunotherapy
Volume10
Issue number5
StatePublished - 1991

Fingerprint

Levamisole
Neoplasm Antigens
Fluorouracil
Monocytes
Colorectal Neoplasms
In Vitro Techniques
2',5'-Oligoadenylate Synthetase
HLA-DP Antigens
Tissue Donors
Indoleamine-Pyrrole 2,3,-Dioxygenase
HLA-DQ Antigens
Fc Receptors
HLA-DR Antigens
Intercellular Adhesion Molecule-1
Lymphocyte Activation
Polyps
Interleukin-2
Blood Cells
Neoplasms
Tumor Necrosis Factor-alpha

Keywords

  • 5-Fluorouracil
  • Duke's C colorectal carcinoma
  • Levamisole

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Pharmacology

Cite this

Schiller, J. H., Lindstrom, M., Witt, P. L., Hank, J. A., Mahvi, D., Wagner, R. J., ... Borden, E. C. (1991). Immunological effects of levamisole in vitro. Journal of Immunotherapy, 10(5), 297-306.

Immunological effects of levamisole in vitro. / Schiller, J. H.; Lindstrom, M.; Witt, P. L.; Hank, J. A.; Mahvi, D.; Wagner, R. J.; Sondel, P.; Borden, E. C.

In: Journal of Immunotherapy, Vol. 10, No. 5, 1991, p. 297-306.

Research output: Contribution to journalArticle

Schiller, JH, Lindstrom, M, Witt, PL, Hank, JA, Mahvi, D, Wagner, RJ, Sondel, P & Borden, EC 1991, 'Immunological effects of levamisole in vitro', Journal of Immunotherapy, vol. 10, no. 5, pp. 297-306.
Schiller JH, Lindstrom M, Witt PL, Hank JA, Mahvi D, Wagner RJ et al. Immunological effects of levamisole in vitro. Journal of Immunotherapy. 1991;10(5):297-306.
Schiller, J. H. ; Lindstrom, M. ; Witt, P. L. ; Hank, J. A. ; Mahvi, D. ; Wagner, R. J. ; Sondel, P. ; Borden, E. C. / Immunological effects of levamisole in vitro. In: Journal of Immunotherapy. 1991 ; Vol. 10, No. 5. pp. 297-306.
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AB - Levamisole, an antihelminthic drug with immunological properties, has recently been reported to have antitumor activity when administered with 5-fluorouracil in patients with Duke's C colorectal carcinoma. The mechanism of this antitumor effect is unknown, but has been postulated to be related to levamisole's immunomodulatory properties. To define further the immunomodulatory activities of levamisole, we studied the in vitro effects of levamisole on monocyte and lymphocyte cytotoxicity, activation, and proliferation; induction of cytokine-induced proteins; and expression of tumor-associated antigens. Experiments utilized peripheral blood mononuclear cells from normal donors incubated in the presence of increasing concentrations of levamisole (0.1 to 100 μg/ml). Levamisole had no consistent effect on induction of 2',5'-oligoadenylate synthetase activity or indoleamine-2,3-dioxygenase activity, or production of tumor necrosis factor. Levamisole had no effect on monocyte cytotoxicity or expression of HLA-DR, HLA-DQ, HLA-DP, and the Fc receptor. Similarly, levamisole had no significant effect on NK or LAK cytotoxicity or the immunological activation of T-lymphocytes, assessed by expression of CD3, CD4, CD8, CD16, CD25, and CD56. Proliferation of lymphocytes from normal donors, patients with benign polyps, and patients with malignancies, with or without IL-2 or irradiated LS174T cells, was not significantly increased overall. No significant enhancement in the expression of three tumor-associated antigens (880364, NRCO-4, and ING-1) and the intercellular adhesion molecule-1 (ICAM-1) antigen on four human cancer cell lines was observed following in vitro exposure to levamisole. We conclude that levamisole is not a potent modulator of the immune parameters we examined, and that the mechanism behind the unique clinical interaction between levamisole and 5-fluorouracil in colorectal carcinoma remains to be identified.

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