Growth hormone prevents human immunodeficiency virus–induced neuronal p53 expression

Growth hormone (GH) is neuroprotective, presumably through its actions on GH receptor–mediated pathways. Here, we examined the effects of GH using in vitro and in vivo assays of human immunodeficiency virus (HIV)–induced neuronal injury. Neuronal cultures were in assays of neurotoxicity induced by supernatants from HIV-1 tat-transfected monocytoid cells (Tat supernatant). GH treatment reduced neuronal death compared with untreated cultures (p < 0.001), which was blocked by a GH receptor antagonist, B2036. Tat supernatant–induced p53 expression in neurons was also reduced by GH treatment. Expression of both p53 and GH receptor were increased in brain tissue from HIV-infected persons compared with controls (p < 0.05). Mice receiving intrastriatal implants of Tat supernatant and treated with GH showed less neurobehavioral abnormalities together with reduced neuroinflammation and neuronal injury compared with untreated animals (p < 0.01). Three acquired immunodeficiency syndrome–defined patients with neurocognitive impairment were serially evaluated during daily GH treatment showing a sustained improvement in neuropsychological performance (p < 0.01). GH prevents neuronal death through its actions on neurons involving a p53-mediated pathway and also improved in vivo neurological function, indicating that GH may have a role in the treatment of HIV-induced neurodegeneration. Ann Neurol 2003;54:605– 614 Human immunodeficiency virus type 1 (HIV-1) infection frequently is associated with the development of neurocognitive impairment in patients during advanced infection, 1 resulting in increased disability and in a poor survival prognosis. 2 HIV-1 principally infects macrophages and microglia but not neurons, resulting in encephalitis and neuronal death that culminates in minor cognitive and motor deficit and HIV-associated dementia (HAD) (reviewed in Power 3 ). Various neuroprotective strategies have been attempted in HIV infection with limited success in terms of neuronal defense and possible recovery, 4 including the use of highly active antiretroviral therapy and select neuroprotective agents. 5 The mechanisms underlying neuronal injury