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Inhibition of Mitogen-Induced Lymphocyte Transformation by Local Anesthetics¹

From the Department of Surgery, University of Minnesota Hospitals, Minneapolis, Minnesota 55455

Abstract

Chlorpromazine (CPZ) and lidocaine were added to cultures of mouse spleen cells stimulated by concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). Concentrations of CPZ greater than 5 x 10^-6M and concentrations of lidocaine greater than 2 x 10^-3M totally inhibited the mitogenic responses to all four mitogens. Minimal inhibitory concentrations of neither drug interferred with cell viability as determined by trypan blue uptake or ⁵¹Cr release. The effects were totally reversed by the removal of the drugs from the culture. Addition of the drug at intervals after mitogen exposure demonstrated that the inhibited event occurred relatively soon after exposure to the mitogen. For example, the addition of lidocaine or CPZ more than 24 hr after Con A stimulation had no effect on tritiated thymidine incorporation. Elevated concentrations of cyclic AMP, cyclic GMP (or their derivatives) or calcium ions could not reverse the local anesthetics inhibition. The known membrane active actions of these drugs and the rapid reversibility of the effect strongly support the idea that the local anesthetics act on the surface membrane of lymphocytes. Binding of radiolabeled Con A or LPS to lymphocyte membranes in the presence of lidocaine or CPZ was not inhibited. The possibility exists that CPZ and lidocaine disorganize cell membranes so as to interfere with the surface membrane elaboration or action of a second messemger, or interfere with cell-cell interactions.

Footnotes

¹ This work was supported by Grants CA 11605 and AI 12754 from the United States Public Health Service.

² Dr. Ferguson is a NCI Fellowship Recipient (CA 02852-02).

³ Address reprint requests to: Dr. Ferguson, Department of Surgery, Box 18, Mayo Memorial Bldg., University of Minnesota Hospitals, Minneapolis, Minnesota 55455.

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