ATLA::Alternatives to Laboratory Animals

Volume 23, Number 2

Evaluation of the immunotoxicity of antiretroviral drugs using an in vitro method for the induction and measurement of a specific antibody response in human peripheral blood lymphocytes.

ATLA 23, 191-196, March/April 1995

Alma L. Luzzati, Elena Giacomini and Luciana Giordani

Department of Immunology, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy

SUMMARY

We studied the effects of the antiretroviral drugs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC) on the induction of a specific primary antibody response to the antigen SRC and on Pokeweed mitogen-induced polyclonal immunoglobulin (Ig) production in cultures of normal human peripheral blood Iymphocytes.

The results presented here show that AZT and DDC inhibited both systems in a dose-dependent way. However, inhibition of the antigenspecific antibody response occurred at drug concentrahons significantly lower than those effective on the mitogen-driven polyclonal response. This was particularly striking for DDC, which was approximately 100 times more powerful, on a molar basis, on the specific antibody response than on polyclonal Ig production. Thus, in vitro systems for the induction of antigen-specific antibody responses in human Iymphocytes may be important, sensitive tools for preclinical studies of the immunotoxicity of antiretroviral drugs.

Keywords: immunotoxicity, HIV antiretroviral drugs, specific antibody response, normal human Iymphocytes