Interleukin-6 expression in primary macrophages infected with human immunodeficiency virus-1 (HIV-1).
We have investigated the effects of human immunodeficiency virus type-1 (HIV-1) infection on constitutive and lipopolysaccharide (LPS)-induced expression of interleukin-6 (IL-6) in cultured blood monocyte-derived macrophages. Highly productive and cytopathic infection of macrophages was established with the macrophage-tropic HIV-1 BaL strain. On Days 14-28 post infection, infected and mock-infected cells were activated with LPS or control medium for 6-24 hours before harvesting culture supernatants and cellular RNA. IL-6 bioactivity in culture supernatants was measured with the IL-6-dependent B9 cell line. IL-6 mRNA levels were quantitated by Northern blot analysis with scanning densitometry. In the absence of LPS activation, IL-6 activity was near or below the limit of detection in supernatants from both infected and uninfected cultures. Similarly, without LPS stimulation, IL-6 mRNA was not detectable in either infected or uninfected macrophages. After activation with LPS, marked increases in IL-6 mRNA levels and supernatant bioactivity were evident in both infected and uninfected cultures, but the response to LPS was consistently greater in infected macrophages. LPS-induced IL-6 mRNA levels and supernatant bioactivity were 7.4- and 4.4-fold higher, respectively, in infected compared with uninfected macrophages (n = 5, p less than .05). These studies demonstrate that highly productive HIV-1 infection does not increase constitutive IL-6 expression in macrophages, but does prime macrophages for an augmented IL-6 response to LPS. These findings may help define the mechanisms responsible for increased IL-6 production in patients with HIV-1 infection.
Department of Rheumatology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA.
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HX
Gan
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Ruef
B F
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Hall
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Tobin
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Remold
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Mellors
D002478:Cells, Cultured; D015726:Giant Cells; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000378:metabolism; D014779:Virus Replication
D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger