Antiretroviral agents increase NO production in gp120/IFNγ-stimulated cultures of rat microglia via an arginase-dependent mechanism

In the present study we carried out a screening of different Antiretroviral drugs (ARVs) for their potential pro-inflammatory effects on microglial cells. Efavirenz, neviparine, darunavir and atazanavir increased nitric oxide (NO) production in microglial cells activated with Gp120CN54 and interferon-γ. The stimulatory effect on NO production appeared to be mediated by inhibition of arginase (ARG) I activity. Consistently the ARG inhibitor, Nω-hydroxy-nor-arginine, mimicked the effects of ARVs. Take together these data suggest that ARG is an additional molecular target of different ARVs, whose inhibition can contribute to their pharmacological activity as well as explain the neurotoxic potential.