Type I interferons (IFN-α and -β) suppress cytotoxin (tumor necrosis factor-α and lymphotoxin) production by mitogen-stimulated human peripheral blood mononuclear cells

Publisher Website
Google Scholar
Abstract
We studied the effect of the different types of interferons on the production of cytotoxin by human peripheral blood mononuclear cells (PBMCs) stimulated with the mitogen phytohemagglutinin (PHA). Maximum secreted levels of cytotoxin were observed at day 3 in culture and consisted of both tumor necrosis factor α (TNF-α) and lymphotoxin as determined by specific antibodies. Type I interferons (IFN-α and IFN-β) consistently suppressed cytotoxin production. Both TNF-α and lymphotoxin were significantly suppressed. Mean suppression by IFN-α and IFN-β (1000 U/ml) was 56 and 66%, respectively, in PBMCs from 18 different donors. The suppressive effects of IFN-α and IFN-β on cytotoxin production were dose responsive over a range of 10 to 1000 U/ml. Type II interferon (IFN-γ) did not have consistent significant effects. Pretreatment with IFN-α or IFN-β for 24 or 48 h prior to PHA stimulation also resulted in significant suppression. Supplementation with interleukin-2 (10 U/ml) or IFN-γ (1000 U/ml) did not overcome cytotoxin suppression by IFN-α or IFN-β. Cytotoxin suppression by IFN-α and IFN-β together appeared to be noninteractive. Suppression appeared not to be due to blockade of the cytotoxin release, since both cell-associated cytotoxin and secreted cytotoxin were suppressed to the same level. These results demonstrated that cytotoxin and lymphotoxin production by PHA-stimulated PBMCs could be down-regulated by type I interferons and that there is a substantial difference between the action of type I interferons and type II interferons (IFN-γ) in modulating the biosynthesis of cytotoxins.

This publication has 0 references indexed in Scilit: