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.
Sathe
S S
SS
Div. of Infectious Diseases, Brooklyn VA Medical Center, NY 11209.
Sarai
A
A
Tsigler
D
D
Nedunchezian
D
D
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