Inhibition of human NK cell function by valinomycin, a toxin from Streptomyces griseus in indoor air

Streptomyces griseus strains isolated from indoor dust have been shown to s ynthesize valinomycin. In this report, we show that human peripheral blood lymphocytes treated with small doses (30 ng ml(-1)) of pure valinomycin or high-pressure liquid chromatography-pure valinomycin from S. griseus quickl y show mitochondrial swelling and reduced NK cell activity, Larger doses (> 100 ng/ml(-1)) induced NK cell apoptosis within 2 days. Within 2 h, the tox in at 100 ng ml(-1) dramatically inhibited interleukin-15 (IL-15)- and IL-1 8-induced granulocyte-macrophage colony-stimulating factor and gamma interf eron (IFN-gamma) production by NK cells. However, IFN-gamma production indu ced by a combination of IL-15 and IL-18 was somewhat less sensitive to vali nomycin, suggesting a protective effect of the cytokine combination against valinomycin. Thus, valinomycin in very small doses may profoundly alter th e immune response by reducing NK cell cytotoxicity and cytokine production.