Inhibition of human lymphocyte proliferation and interleukin 2 production by platelet activating factor (PAF-acether]: Reversal by a specific antagonist, BN 52021

Abstract

When added to a 72 h culture of human peripheral blood mononuclear leukocytes stimulated with phytohemagglutinin, PAF-acether caused a significant inhibition (40–65%) of proliferation at concentrations of 10 −8 to 10 −6M. This inhibition was reversed by the specific PAF antagonist, BN 52021. It was also reversed by indomethacin, suggesting that PAF-acether mediated this suppression via cyclooxygenase metabolites of arachidonic acid. IL-2 production, measured at 24 h of lymphocyte proliferation, was similarly impaired [50–66%] by 10 −8–10 −6M PAF-acether. IL-2 production was brought up to 90% of control values when both PAF-acether and BN 52021 (10 −4M) were added together to the lymphocyte cultures. These studies suggest a significant immunoregulatory role for PAF-acether and a potential use of BN 52021 as a biological response modifier.