Inflammatory cytokines and HIV-1-associated neurodegeneration: Oncostatin-M produced by mononuclear cells from HIV-1-infected individuals induces apoptosis of primary neurons

Neurologic abnormalities are common in HIV-1-infected patients and often re present the dominant clinical manifestation of pediatric AIDS. The neurolog ical dysfunction has been directly related to CNS invasion by HIV-1 that is principally, if not exclusively, supported by blood-derived monocytes/macr ophages and lymphocytes, By using primary long term cultures of human fetal sensory neurons as well as sympathetic precursors-like neuronal cells, we determined that blood-derived mononuclear cells from HIV-1-infected individ uals spontaneously release soluble mediators that can potently inhibit the growth and survival of developing neurons as well as the viability of postm itotic neuronal cells by inducing apoptotic cell death. Analysis of the cyt okines produced by lymphomonocytic cells, HIV-1 infected or activated, indi cated that oncostatin M (oncM) is a major mediator of these effects. Since low TGF-beta 1 concentrations were capable of enhancing oncM-mediated neuro nal alterations, our data indicate that by acting in concert with other cyt okines, oncM may induce neuronal demise in both the developing and the matu re brain. Thus, this cytokine may contribute to the setting of the neuronal cell damage observed in HN-l-infected individuals.