Growth inhibition of Mycobacterium avium complex in human alveolar macrophages by the combination of recombinant macrophage colony-stimulating factor and interferon-gamma.
The reservoir of Mycobacterium avium complex (MAC) during human infection is the mononuclear phagocyte. In these studies, the ability of certain macrophage-active cytokines to affect MAC growth in human alveolar macrophages was evaluated. Neither recombinant interferon-gamma (2 x 10(2) to 10(3) U/well of 5 x 10(5) cells) nor recombinant macrophage colony-stimulating factor (20 to 50 ng/well), when tested alone, exhibited a consistent ability to induce macrophage targets to inhibit the growth of a clinical strain of MAC serovar 4. However, the combination of these cytokines (1 to 50 ng macrophage colony-stimulating factor + 10(3) U interferon per well) was remarkably effective in diminishing replication of MAC in all experiments. These cytokines were also able to induce alveolar macrophages to restrict MAC growth even though cells were obtained from several individuals with acquired immunodeficiency syndrome (AIDS) or from normal donors and infected in vitro with the human immunodeficiency virus type 1. The effect of this cytokine combination was not abrogated by 10(4) neutralizing U/ml of anti-tumor necrosis factor-alpha antibody. Rather, the combination of interferon-gamma and macrophage colony-stimulating factor appeared to activate intrinsic macrophage mechanisms for restricting MAC growth and deserves further study to determine the potential value of this cytokine combination in the treatment of human infection.
Rose
R M
RM
Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts 02215.
Fuglestad
J M
JM
Remington
L
L
D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology*; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000254:growth & development; D011650:Pulmonary Alveoli / Q000166:cytology / Q000382:microbiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma