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Activation of monocyte-mediated tumoricidal activity in patients with acquired immunodeficiency syndrome
Authors:E S Kleinerman  L M Ceccorulli  L A Zwelling  T Twilley  R B Herberman  J Jacob  E P Gelmann
Abstract:The purpose of these studies was to determine whether peripheral blood monocytes from acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma could be activated to lyse human tumor target cells in vitro. Monocytes were isolated and incubated for 24 hours in vitro with either medium (control), a crude mitogen-induced lymphokine preparation (MAF), or endotoxin before the addition of [125I]IUdR-labeled A375 melanoma target cells. Cytolysis was determined 72 hours later. Twelve (100%) of 12 patients tested had monocyte-mediated cytotoxicity values that were comparable to those of normal individuals. Recombinant human gamma interferon (IFN gamma) activated both normal and AIDS monocyte-mediated tumoricidal function only when combined with lypopolysaccharide (LPS). In addition, mononuclear cells from ten AIDS patients were also tested for their ability to secrete MAF and IFN gamma in response to a mitogenic stimulus. Lymphokines generated from all ten patients contained substantial amounts of IFN gamma (100 to 2,500 U/mL); however, three of these ten lymphokine preparations failed to activate normal monocytes to lyse tumor cells. These results suggest that monocyte-mediated tumoricidal function of AIDS patients is intact and thus suggest new approaches for the therapy of AIDS.
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