In vitro lymphotoxicity and selective t cell immunotoxicity of high doses of acyclovir and its derivatives in mice

• Published in: International journal of immunopharmacology Vol. 18; no. 6; pp. 429 - 438
• Main Authors: Poluektova, L., Krzystyniak, K., Desjardins, R., Flipo, D., Fournier, M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 01.06.1996
• Subjects: acyclovir; Acyclovir - analogs & derivatives; Acyclovir - toxicity; Animals; Antigens, Surface - analysis; Antigens, Surface - biosynthesis; Antiviral Agents - toxicity; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Cell Survival - drug effects; Cells, Cultured; cytometric assay; Female; Immunomodulators; immunopharmacology; immunotoxicity; in vitro lymphotoxicity; lymphocyte subsets; Medical sciences; Mice; Mice, Inbred C57BL; mouse lymphocyte; Pharmacology. Drug treatments; Phytohemagglutinins - pharmacology; Spleen - cytology; Spleen - drug effects; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; lymphocyte subsets; cytometric assay; in vitro lymphotoxicity; immunotoxicity; immunopharmacology; acyclovir; mouse lymphocyte; Cell culture; Acyclic nucleoside; Purine nucleoside; Rodentia; Cytotoxicity; In vitro; Cell subpopulation; Biological activity; Cytometry; In vivo; Vertebrata; Mammalia; Mouse; Animal; T-Lymphocyte; Aciclovir; Antiviral; Immunosuppressive agent
• ISSN: 0192-0561; 1879-3495
• DOI: 10.1016/S0192-0561(96)00017-3

The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N 2-acetyl ACV (ac-ACV) and N 2,O-diacetyl ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute number of CD3 +, CD8 +, and CD25 + cells, but not Ig + cells, was noted at high concentrations of ACV and its derivatives, suggesting a selective T cell cytotoxicity. Similarly, the in vivo exposure revealed selective T cell immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2 + and CD8 + cells was not accompanied with any marked changes in the Ig + population. The CD4 +/CD8 + ratio was affected both in vitro and in vivo by high concentrations of ACV.