The ability of spleen cells treated with
methionine enkephalin (Met-ENK) in the presence of
3'-azido-3'-deoxythymidine (AZT) to produce
cytokines and inhibit Friend
leukemia virus (FLV) replication in Mus dunni cell cultures was investigated. In the presence of murine spleen cells, combination treatments using AZT plus Met-ENK or
concanavalin A reduced FLV replication by 63% and 84%, respectively, as compared with 47% for AZT alone. When
interleukin (IL)-2,
IL-4 and
interferon (IFN gamma) levels were measured in FLV-infected cell cultures, both AZT and Met-ENK treatments induced a higher production of IFN gamma and a slight increase in
IL-2 and
IL-4, as compared with either treatment alone. Subsequent treatment of FLV-infected cells with
concanavalin A-stimulated cell supernatants, containing approximately 10 U/ml each of IFN gamma and
IL-2, resulted in inhibition of viral replication. Thus, in the absence of spleen cells, IFN gamma was added to cell cultures to determine whether this
cytokine contributed to combination
antiviral effects. Results show that addition of IFN gamma alone results in a slight suppression of FLV expression, whereas treatment with both AZT and IFN gamma inhibits FLV replication significantly. Subsequently, addition of anti-IFN gamma antibody to cell cultures treated with Met-ENK blocked
antiviral effects due to this
neuropeptide. Thus anti-FLV effects of spleen cells treated with Met-ENK in combination with AZT are mediated to a large degree by IFN gamma.