13 native human interferon-alpha species assessed for immunoregulatory properties

Abstract

Human leukocytes treated with Sendai virus yield interferon predominantly of the alpha-type (HuIFN-alpha). Successful attempts to purify these "native" species have been performed and the final analysis, which included an SDS-PAGE disclosed 13 stained and separated IFN-proteins in the molecular weight-range of 16.6-23.5 kD. These stained IFN proteins were eluted individually from the gel slices and assessed for antiviral activity in human, monkey, and bovine cells, as well as for immunomodulatory effects (in vitro) on human lymphocytes. Based on equal amounts of (human) IFN units, as determined by IFN titration on human cells, the "immunological efficacies" of the 13 different HuIFN-alpha species were determined in three different immunological systems with the following results: (1) Augmentation of the NK function was a property of all species, although the two lower species (16.6 kD, 16.9 kD) were clearly less efficient with "titers" in the NK system reduced 25-fold. (2) Enhanced expression of HLA on lymphocyte membranes was induced by all the HuIFN-alpha species to the same extent. (3) Addition of IFN to mixed lymphocyte reaction (MLR) augmented the CML outcome of the cultures. In this system all 13 species exerted their effect equally well; no clear inferiority or superiority of individual species were seen. It is concluded that the fractionation of the IFN-alpha into 13 species does not give rise to IFN species which are specific only for some functions and not for others. All species exert all functions, although the relatively "immunological" titers in the NK system varied within the species.