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.
Bibliographical noteFunding Information:
The authors thank Edna Cohen, Anna Itzik, Shiri Lavi, Nadav Mishaan, and Einav Orion and for their assistance in conducting the experiments. IL-1ra was generously provided by Amgen, Thousand Oaks, CA, USA. Recombinant rat IL-10 was generously provided by Dr. Stephen Poole. RrIL-10 was produced within the context of the Biomed Concert Action Cytokines in the Brain. R.Y. is a member of the Eric Roland Center for Neurodegenerative Diseases of The Hebrew University of Jerusalem. This work was supported by a grant 97-204 from the US–Israel Binational Science Foundation.
- Sickness behavior