Effects of Immunomodulatory Drugs on T Lymphocyte Activation and Function

During this third reporting year 51588 to 51489, the following drugs were tested for their immunomodulatory actions. Acridine trihydrochloride CL246, OK432, WY18251, poly ICLC AVS1761, Quinolinamine AVS1300, and Ampligen AVS2149. These drugs were tested for their effects on the production of antibody that is stimulated upon addition of Pokeweed Mitogen PWM to lymphocyte cultures or upon infection of lymphocytes with Epstein-Barr Virus EBV. The drugs were also tested for their effects on lymphocyte proliferation stimulated by EBV. Finally, the drugs were tested for their ability to modulate the generation of lymphokine activated killer cells LAK which are stimulated upon culturing T lymphocytes with Interleukin 2 IL2. We found that Acridine trihydrochloride had a pronounced inhibitory effect on all of the above tested functions. This inhibition was most pronounced with drug concentrations above 0. 1 micro gml. Quinolinamine at concentrations above 0.1 micro gml stimulated both the PWM-stimulated lgM and lgG production, as well as the EBV-induced proliferation of lymphocytes. This drug had also a small, but significant augmenting effect on EBV-induced lgM production at 1 micro gml without, however, affecting the virus-induced lgG production. Finally, at low concentrations 0.001-1 micro gml Quinolinamine stimulated the induction of LAK cells while at higher concentrations 2.5-20 micro gml inhibited their production