In vivo enhancement of murine natural killer cell activity by 7-allyl-8-oxoguanosine (loxoribine)

Abstract

7-Allyl-8-oxoguanosine (loxoribine) is a novel immunostimulatory compound which has been shown previously to enhance the antibody synthesis of antigen-stimulated B-lymphocytes. In this report, loxoribine was tested for the ability to activate murine natural killer (NK) cells. In studies in which mice were given a single subcutaneous (s.c.) or intravenous (i.v.) injection of loxoribine, splenic NK cell activity was increased in a dose-related manner with clear enhancement seen within 2 h of drug administration. The enhancement was optimal at 48 h but persisted for a minimum of 4 days. Slow and continuous administration of loxoribine via subcutaneously implanted infusion pumps successfully enhanced the NK activity for several days after all of the pump contents had been delivered. Peak NK responses were seen following s.c. or i.v. administration of 2–3 mg loxoribine per mouse in sesame oil, intralipid, or saline vehicles. Significant oral activity was seen after the administration of 8–10 mg/mouse in sesame oil or intralipid. The in vivo enhancement of NK activity was observed in spleen, blood, and bone marrow but was negligible in lymph nodes and thymus. Multiple injections of optimal concentrations of loxoribine did not tend to enhance the NK activity above that seen with a single injection, suggesting that the timing of injections was critical for optimal responsiveness.