Inhibition of human LAK-cell activity by the anti-depressant trifluoperazine

• Published in: Immunopharmacology Vol. 29; no. 1; pp. 1 - 10
• Main Authors: DE LA ROCQUE, L, CAMPOS, M. M, BENI OLEJ, CASTILHO, F, MEDIANO, I. F, RUMJANEK, V. M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.02.1995
• Subjects: Antigens, Differentiation, T-Lymphocyte - drug effects; Antigens, Differentiation, T-Lymphocyte - genetics; Binding, Competitive; Biological and medical sciences; Cell Division - drug effects; Dipeptidyl Peptidase 4 - biosynthesis; Drug toxicity and drugs side effects treatment; Flow Cytometry; Humans; Immunosuppression; Interleukin-2 - pharmacology; Killer Cells, Lymphokine-Activated - drug effects; Killer Cells, Natural - drug effects; Leukemia, Erythroblastic, Acute - pathology; Leukemia, T-Cell - pathology; Lymphocyte Activation - drug effects; Lymphocyte Activation - genetics; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Mitogens - pharmacology; Pharmacology. Drug treatments; Receptors, Interleukin-2 - biosynthesis; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Trifluoperazine - toxicity; Tumor Cells, Cultured; Natural killer cell; Human; Cell proliferation; Cell culture; Neuroleptic; Psychotropic; Immunotherapy; Leukemia; LAK cell; Cytotoxicity; Phenothiazine derivatives; In vitro
• ISSN: 0162-3109
• DOI: 10.1016/0162-3109(95)00037-T

The anti-depressive drug trifluoperazine (TFP) was studied on in vitro immune responses. TFP proved to be an inhibitor of lymphokine-activated killer (LAK) cells in its generative step, as well as in its effector phase. Natural killer (NK) activity and interleukin-2 (IL-2) or mitogen-induced lymphocyte proliferation were just as sensitive to the drug effects, whereas the division of tumor cells was more resistant. The mechanism through which TFP suppresses these lymphocytic systems remains unclear. It does not, however, affect an early stage of cellular activation as the addition of the drug as late as 24 h after the start of the culture was still inhibitory for lymphocyte mitogenesis. Neither the expression of CD25, nor that of CD56 was affected by TFP, and exogenous IL-2 was unable to overcome the suppression of proliferation. In relation to cell-mediated cytotoxicity, TFP partially interfered with the effector/target binding. However, addition of lectin to the assay did not overcome the inhibition of lysis produced by the drug. Although further work remains to be done, the effect of TFP on immune responses must be taken into consideration when treating immunosuppressed patients.