Sw. Cole et al., NOREPINEPHRINE ACCELERATES HIV REPLICATION VIA PROTEIN-KINASE A-DEPENDENT EFFECTS ON CYTOKINE PRODUCTION, The Journal of immunology (1950), 161(2), 1998, pp. 610-616
To explore the role of sympathetic nervous system activation in HIV pa
thogenesis, we examined the effect of the neuroeffector molecule norep
inephrine (NE) on HIV-1 replication in quiescently infected PBMCs that
were subsequently activated with Abs to CD3 and CD28. NE accelerated
HIV-1 replication at concentrations ranging from 10(-8) to 10(-5) M. T
his effect could be mimicked by protein kinase A (PKA) activators (for
skolin or dibutyryl-cAMP) and abrogated by beta-adrenoreceptor antagon
ists or the PKA inhibitor rp-cAMP, indicating transduction via the adr
enoreceptor signaling pathway, NE reduced cellular activation and alte
red the production of several HIV-modulating cytokines: IL-10 and IFN-
gamma were markedly suppressed; TNF-alpha, IL-1 beta, IL-2, IL-4, and
IL-6 mere mildly suppressed; and levels of IL-12 were nest significant
ly altered. The addition of either exogenous IFN-gamma or IL-10 abroga
ted tale effect of NE on virus production Thus PKA-dependent suppressi
on of cytokine production appears to mediate the enhancement of HIV-1
replication by NE.