Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis

• Published in: Journal of neuroimmunology Vol. 115; no. 1; pp. 182 - 191
• Main Authors: Zhao, Meng-Liang, Kim, Mee-Ohk, Morgello, Susan, Lee, Sunhee C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 02.04.2001
• Subjects: Adult; AIDS; AIDS Dementia Complex - complications; AIDS Dementia Complex - metabolism; AIDS Dementia Complex - pathology; Astrocyte; Astrocytes - metabolism; Astrocytes - pathology; Brain - metabolism; Brain - pathology; Brain - virology; Caspase 1 - biosynthesis; caspase-1; Cytokine; Dementia; Encephalitis, Viral - etiology; Encephalitis, Viral - metabolism; Encephalitis, Viral - pathology; Female; HIV Core Protein p24 - metabolism; HIV Envelope Protein gp41 - metabolism; human immunodeficiency virus 1; Humans; Immunohistochemistry; Interleukin-1 - biosynthesis; Macrophages - metabolism; Macrophages - pathology; Male; Microglia; Microglia - metabolism; Microglia - pathology; Middle Aged; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; AIDS; Astrocyte; Cytokine; Microglia; Dementia
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(00)00463-X

Inflammatory cytokines and enzymes such as IL-1 and inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of AIDS dementia, a condition associated with infection of the CNS cells by the HIV-1. In this report, we investigated the expression of iNOS, IL-1, and caspase-1 (interleukin-1 converting enzyme) in HIV-1 encephalitis (HIVE) by immunocytochemistry and analyzed their expression with respect to HIV-1 infection and glial activation. In HIVE, all three molecules were expressed at high levels in areas of HIV-1 infection (microglial nodules with HIV-1 p24 immunoreactivity) and in areas of diffuse white matter gliosis. Expression was cell-type specific, with IL-1 and caspase-1 being expressed in macrophages and microglia, and iNOS in activated astrocytes. Multinucleated giant cells, a hallmark of virally infected cells, showed intense staining for both IL-1 and caspase-1, suggesting induction of these molecules by HIV-1. Double immunocytochemistry demonstrated a regional co-localization of astrocyte iNOS and microglial IL-1 and caspase-1. These results support the notion that autocrine and paracrine interactions between HIV-1 infected macrophages and microglia, activated microglia, and astrocytes lead to expression of proinflammatory and neurotoxic molecules. iNOS and caspase-1 may provide additional therapeutic targets for HIVE.