THE ROLE OF INTERFERON-GAMMA IN ANTIRETROVIRAL ACTIVITY OF METHIONINE-ENKEPHALIN AND AZT IN A MURINE CELL-CULTURE

The ability of spleen cells treated with methionine enkephalin (Met-EN K) in the presence of 3'-azido-3'-deoxythymidine (AZT) to produce cyto kines and inhibit Friend leukemia virus (FLV) replication in Mus dunni cell cultures was investigated. In the presence of murine spleen cell s, combination treatments using ATT plus Met-ENK or concanavalin A red uced FLV replication by 63% and 84%, respectively, as compared with 47 % for ATT alone. When interleukin (IL)-2, IL-4 and interferon (IFN gam ma) levels were measured in FLV-infected cell cultures, both AZT and M et-ENK treatments induced a higher production of IFN gamma and a sligh t increase in IL-2 and IL-4, as compared with either treatment alone. Subsequent treatment of FLV-infected cells with concanavalin A-stimula ted cell supernatants, containing approximately 10 U/ml each of IFN ga mma and IL-2, resulted in inhibition of viral replication. Thus, in th e absence of spleen cells, IFN gamma was added to cell cultures to det ermine whether this cytokine contributed to combination antiviral effe cts. Results show that addition of IFN gamma alone results in a slight suppression of FLV expression, whereas treatment with both AZT and IF N gamma inhibits FLV replication significantly. Subsequently, addition of anti-IFN gamma antibody to cell cultures treated with Met-ENK bloc ked antiviral effects due to this neuropeptide. Thus anti-FLV effects of spleen cells treated with Met-ENK in combination with AZT are media ted to a large degree by IFN gamma.