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.