ENHANCEMENT OF NATURAL-KILLER-CELL ACTIVITY IN HUMAN IMMUNODEFICIENCYVIRUS-INFECTED SUBJECTS BY IN-VITRO TREATMENT WITH BIOLOGIC RESPONSE MODIFIER OK-432

A decrease in natural killer (NK) cell function has been related to th e progression of human immunodeficiency virus (HIV) infection, In the present study,we assessed the ability of a streptococcus-derived biolo gic response modifier, OK-432, to augment NK lysis of uninfected K562 and U937 felts and HIV-infected U937 cells by peripheral blood mononuc lear cells (PBMC) from HIV-seropositive homosexual men, Optimal two- t o fourfold increases in lysis of the three targets were observed after pretreatment of PBMC from HN-negative subjects for 4 h with 2 mu g of OK-432 per mi, This effect was related primarily to gamma interferon (IFN-gamma) production induced by OK-432 and was not linked to product ion of tumor necrosis factors alpha and beta or to monocytes in the cu ltures, The enhancing effect of OK-432 on NK cell function was diminis hed but still evident in PBMC from subjects with relatively early-phas e (<3-year) HIV infection and high CD4(+) cell counts and was lower in subjects with longer-term HIV infection (>3 years), in association wi th reduced production of IFN-gamma, Augmentation of NK cell activity i n HIV-infected men by OK-432 was comparable to that induced by treatme nt of cells with 1,000 U of IFN-alpha or interleukin 2 per mi. The dat a suggest that the NK cell-enhancing effects of OK-432 are at least in part mediated by IFN-gamma and that OK-432 may be effective in treatm ent of patients with early-phase HIV infection.