ENHANCEMENT OF NATURAL-KILLER ACTIVITY AND INTERFERON INDUCTION BY DIFFERENT ACYCLIC NUCLEOSIDE PHOSPHONATES

Acyclic nucleoside phosphonate (ANP) analogues are a class of compound s with potent activity against herpesviruses and/or retroviruses. Our preliminary experiments have shown that 9-(2-phosphonylmethoxyethyl)ad enine (PMEA), a prototype of the ANP family, enhances some parameters of natural immunity. In this paper we have evaluated the effect of dif ferent schedules of administration of PMEA and other ANP analogues of clinical interest upon natural killer (NK) activity and interferon (IF N) production in a mouse model. The results show that PMEA significant ly enhances NK activity and interferon production. Other ANP analogues tested in our system, i.e., 9-(2-phosphonylmethoxyethyl)-2,6-diaminop urine (PMEDAP), and 9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPM PA), similarly induced enhancement of natural immunity. The immunomodu lating effect of PMEA was even more pronounced with a single administr ation compared to repeated administrations of the drug. Dose-dependent enhancement of NK activity and IFN production could also be demonstra ted during chronic administration of PMEA (more resembling to what wil l be the schedule of administration of this drug in patients). Overall , the data here presented suggest that the enhancement of some natural immune functions induced by ANP analogues may add to the direct antiv iral activity of these drugs against retroviruses and herpesviruses, a nd thus may be able to increase the host resistance against viral infe ctions.