Pentoxifylline aggravates impairment in tumor necrosis factor-alpha secretion and increases mycobacterial load in macrophages from AIDS patients with disseminated Mycobacterium avium-intracellulare complex infection.
Pentoxifylline, which inhibits tumor necrosis factor-alpha (TNF alpha), decreases human immunodeficiency virus replication in peripheral blood mononuclear cells. However, TNF alpha is important in cellular defense against M. avium-intracellulare complex (MAC), a common infection in advanced AIDS. The effect of pentoxifylline on mycobacterial colony counts in macrophages with in vivo MAC infection was evaluated, and differences in lipopolysaccharide (LPS)-induced TNF release in infected and uninfected macrophages were determined. Macrophages with in vivo MAC infection released much less TNF alpha in response to LPS (P = .01). The response was partially restored after antimycobacterial therapy. Pentoxifylline, in a concentration that inhibited LPS-induced TNF alpha by 52.4%, increased MAC counts by 2.5- to 50.0-fold. Thus, macrophages from AIDS patients with disseminated MAC infection are deficient in their ability to release TNF alpha, and further inhibition by pentoxifylline may be detrimental.
Div. of Infectious Diseases, Brooklyn VA Medical Center, NY 11209.
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Sathe
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Sarai
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Tsigler
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Nedunchezian
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D015169:Colony Count, Microbial; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy / Q000276:immunology*; D010431:Pentoxifylline / Q000009:adverse effects* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline