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Related Experiment Videos

Human immunodeficiency virus glycoprotein (gp120) infused into rat brain induces interleukin 1 to elevate

S K Sundar1, M A Cierpial, L S Kamaraju

  • 1Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.

Proceedings of the National Academy of Sciences of the United States of America
|December 15, 1991
PubMed
Summary

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Human immunodeficiency virus (HIV) envelope protein gp120 induces interleukin 1 (IL-1) in rat brains, potentially causing AIDS-related abnormalities. This IL-1 induction is specific to the brain and not from contaminants or systemic effects.

Area of Science:

  • Neuroimmunology
  • Virology
  • Endocrinology

Background:

  • The human immunodeficiency virus (HIV) envelope protein gp120 is implicated in neurological complications. Interleukin 1 (IL-1) is a key inflammatory mediator in the central nervous system.
  • Understanding the direct effects of HIV proteins on brain cytokine production is crucial for explaining HIV-associated neuroinflammation and cognitive deficits.

Purpose of the Study:

  • To investigate whether intracerebroventricular (i.c.v.) infusion of HIV gp120 induces interleukin 1 (IL-1) in the brain.
  • To determine if gp120-induced IL-1 in the brain is responsible for associated physiological changes, such as altered endocrine and immune responses.

Main Methods:

  • Rats received i.c.v. infusions of glycosylated recombinant gp120 or control substances. Brain glial lysates were analyzed for IL-1 activity using thymocyte stimulation assays.

Related Experiment Videos

  • Plasma steroid levels and immune cell activities (NK cell, mitogenic response) were measured. Effects of co-infusion with alpha-melanocyte-stimulating hormone were assessed. LPS-resistance and heat-inactivation experiments were performed to rule out contamination. Direct hippocampal injections were also conducted.

    • Main Results:

    • i.c.v. gp120 infusion detected IL-1 activity in 61% of rat brains, compared to 4% in controls. IL-1 was detected at 2, 6, and 24 hours post-infusion.
    • gp120 infusion elevated plasma steroids and decreased immune cell activities, effects blocked by alpha-melanocyte-stimulating hormone. These effects were specific to i.c.v. administration, not seen with intravenous gp120.
    • gp120-induced IL-1 was not due to LPS contamination and occurred in LPS-resistant mice. Direct hippocampal injection was more potent than i.c.v. infusion. Monoclonal antibodies blocked gp120-induced thymocyte stimulation.

    Conclusions:

    • Intracerebroventricular administration of HIV gp120 directly induces IL-1 production within the brain.
    • This gp120-induced brain IL-1 contributes to neuroendocrine and immune alterations observed in HIV infection, potentially explaining some AIDS-related abnormalities.
    • These findings highlight a direct mechanism by which HIV can trigger inflammatory responses in the central nervous system, contributing to pathogenesis.