PATHOGENESIS AND CYTOKINES IN HIV SENSORY NEUROPATHY

Project: Research project

Description

The central and peripheral nervous system and the immune system are
primary targets for human immunodeficiency virus type 1 (HIV-1) infection
in individuals with acquired immunodeficiency syndrome (AIDS). The
pathogenesis of the peripheral neuropathy has not been elucidated. The
structural features of the peripheral sensory system offers the
possibility to determine the exact mechanism by which neuronal damage is
produced by HIV-1, dissecting out the relevant roles of
macrophage/monocytes, HIV-1 infection-of macrophage/monocytes, cytokines
production, and opportunistic viral infections. We will test the hypotheses that the distal progressive sensory
neuropathy of AIDS is 1) A dying back disorder and 2) that humoral
factors or cytokines secreted by macrophages are the likely cause. We
will use immunohistochemistry, PCR techniques and in situ hybridization
to identify cytokine-producing cells in peripheral nervous tissue from
AIDS patients to confirm the identity of the HIV-1 infected cells, and
the presence of opportunistic viruses. Cytokine production will be
correlated with inflammation, neuronal loss, and replication of HIV-1.
Biopsied sural nerve and post-mortem tissues of patients dying with AIDS
and acute death controls will include the sural, tibial and sciatic
nerves, the corresponding L5 and Sl dorsal root ganglia, and the whole
spinal cord. Morphometric analyses will be performed to decide if this
is a true dying back neuropathy or due to the cumulative effects of
multiple peripheral nerve lesions. This proposal capitalizes on the high
incidence of neuropathy among subjects dying with AIDS and will result in
determination whether the incidence and progression of neuropathy among
the AIDS subjects may result from cytokine production by
macrophage/monocytes in situ in DRGs.
StatusFinished
Effective start/end date2/1/931/31/98

Funding

  • National Institutes of Health: $422,745.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $395,961.00
  • National Institutes of Health: $336,005.00

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HIV-1
HIV
Cytokines
Acquired Immunodeficiency Syndrome
Monocytes
Virus Diseases
Macrophages
Sural Nerve
Nerve Tissue
Diagnosis-Related Groups
Opportunistic Infections
Peripheral Nervous System
Spinal Ganglia
Peripheral Nervous System Diseases
Peripheral Nerves
Immune System
Central Nervous System
Immunohistochemistry
Viruses
Inflammation

ASJC

  • Medicine(all)
  • Neuroscience(all)