Antiretroviral nucleoside analogues suppress antibody synthesis in human B-lymphocytes

作者：Setzer Bernhard; Walker Ulrich A^*

来源：Antiviral Therapy, 2012, 17(4): 729-735.

DOI：10.3851/IMP2086

Background: Some antiretroviral nucleoside reverse transcriptase inhibitors (NRTI) impair mitochondrial polymerase-gamma and T-cell proliferation, possibly by pyrimidine depletion. We aimed to analyse NRTI effects on the content of mitochondrial DNA (mtDNA) and B-cells, and on their proliferation and antibody synthesis. %26lt;br%26gt;Methods: Peripheral blood B-lymphocytes from six healthy individuals were stimulated in vitro with interleukin-4 and Staphylococcus aureus superantigen in the presence or absence of NRTI in concentrations equivalent to, or fivefold exceeding, human peak plasma levels. We also tested the effects of uridine, a pyrimidine precursor, which has antagonized NRTI toxicities in other models. %26lt;br%26gt;Results: During 9 days of culture, B-lymphocyte proliferation and vitality were not affected by NRTI. Didanosine and stavudine, but not zidovudine, dose-dependently induced mtDNA depletion. All three NRTI significantly and dose-dependently impaired the synthesis of all immunoglobulin classes. The lymphocyto-toxic effects of the thymidine analogues zidovudine and stavudine on B-lymphocytes were antagonized by the addition of uridine. %26lt;br%26gt;Conclusions: Didanosine, stavudine and zidovudine induce mitochondrial toxicity in human B-lymphocytes and impair the immunoglobulin synthesis in vitro, warranting further studies on their in vivo effects.

• 出版日期2012