Am. J. Respir. Cell Mol. Biol., Vol 10, No. 5, May 1994, 580-585.
Modulation of accessory cell function and interleukin-6 production by the HIV-1 tat gene
GK Iwamoto, SA Konicek and HL Twigg 3rd
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Manifestations of HIV-1 infection such as fever, hypergammaglobulinemia,
and interstitial pneumonitis may be due to increased production of
inflammatory cytokines such as interleukin-1 and interleukin-6 (IL-6).
Monocytes/macrophages of HIV-1-infected individuals have been noted to
produce increased amounts of IL-6, as well as to have enhanced accessory
cell function. These studies examined the ability of HIV-1 tat, an
important HIV-1 regulatory gene, to modulate monocyte/macrophage function.
In these experiments, HIV-1 tat-transfected THP-1 cells, a monocytic cell
line, enhanced THP-1 immune accessory cell function in the presence of
pokeweed mitogen and concanavalin A. HIV-1 tat-transfected cells also
increased production of lipopolysaccharide-stimulated IL-6 mRNA and IL-6
protein. The ability of monocytes/macrophages to support HIV-1 production
while exhibiting little or no cytopathic effects allows these cells to
serve as a reservoir for the virus. The ability of HIV-1 tat to regulate
cellular function in monocytes/macrophages may play an important part in
the pathogenesis of HIV-1 infection.
