Involvement of brain cytokines in the neurobehavioral disturbances induced by HIV-1 glycoprotein120

• Published in: Brain research 2002-04, Vol.933 (2), p.98-108
• Main Authors: Barak, Ohr, Goshen, Inbal, Ben-Hur, Tamir, Weidenfeld, Joseph, Taylor, Anna N, Yirmiya, Raz
• Format: Article
• Language: English
• Subjects: AIDS; AIDS Dementia Complex - immunology; AIDS Dementia Complex - metabolism; AIDS Dementia Complex - virology; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Brain - drug effects; Brain - immunology; Brain - virology; Cytokines - drug effects; Cytokines - immunology; Cytokines - metabolism; Drug Interactions - physiology; Enzyme Inhibitors - pharmacology; Experimental viral diseases and models; Gene Expression Regulation, Viral - drug effects; Gene Expression Regulation, Viral - physiology; Gp120; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV Envelope Protein gp120 - pharmacology; Human immunodeficiency virus; Human immunodeficiency virus 1; IL-1; IL-10; Infectious diseases; Injections, Intraventricular; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - genetics; Interleukin-10 - pharmacology; Male; Medical sciences; Nerve Degeneration - immunology; Nerve Degeneration - metabolism; Nerve Degeneration - virology; Neurons - drug effects; Neurons - immunology; Neurons - virology; Pentoxifylline - pharmacology; Rats; Rats, Inbred F344; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Sialoglycoproteins - immunology; Sialoglycoproteins - pharmacology; Sick Role; Sickness behavior; TNFα; Tumor Necrosis Factor-alpha - genetics; Viral diseases
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(02)02280-1

Intracerebroventricular (i.c.v.) administration of HIV-1 glycoprotein 120 (gp120), the envelope protein used by the virus to gain access into immune cells, induces neurobehavioral alterations in rats. To examine the role of proinflammatory cytokines in mediating these effects, we measured the effects of gp120 on brain proinflammatory cytokine expression and the effects of anti-inflammatory agents, including interleukin-1 receptor antagonist (IL-1ra), pentoxifylline (a TNFα synthesis blocker) and IL-10, on gp120-induced sickness behavior. I.c.v. administration of gp120 induced the expression of IL-1β, but not TNFα, mRNA in the hypothalamus, 3 h after the injection. Pretreatment of rats with IL-1ra, but not with pentoxifylline, significantly attenuated gp120-induced anorexia and loss in body weight, whereas both agents had no effect on gp120-induced reduction in locomotor activity in the open field. Pretreatment with either IL-1ra and pentoxifylline simultaneously, or with IL-10, produced effects that were similar to the effects of IL-1ra alone. Together, these findings indicate that IL-1, but not TNFα, mediates some of the behavioral effects of acute gp120 administration, suggesting that brain IL-1 may be involved in some of the neurobehavioral abnormalities evident in AIDS patients.