CYTOKINE DYSREGULATION IN HIV-ASSOCIATED NEUROLOGICAL DISEASE

AIDS is associated with three major neurological syndromes: dementia ( HIVD), vacuolar myelopathy (VM) and plainful sensory neuropathy (PSN). The pathogenesis of these conditions remains unclear although they al l demonstrate a marked increase in macrophage number and activation de spite systemic immunosuppression. It was therefore of interest to dete rmine the profile of cytokine and HIV expression in brain, spinal cord and peripheral nerves of AIDS patients with AD, VM and PSN, as compar ed to AIDS patients without neurological disease and seronegative cont rols. RNA was extracted from brain, spinal cord and peripheral nerve a nd RT/PCR for cytokine and HIV mRNA was performed. In situ RT/PCR was performed to determine the number and type of cells expressing cytokin e message and this was compared to the number of cells containing HIV DNA detected with in situ PCR. We found a consistent profile of increa sed TNF alpha and decreased IFN gamma and IL4 in all three syndromes c ompared to AIDS patients without neurological disease. IL1 did not inc rease in parallel with TNF alpha IL10 was decreased in the VM tissue. HIV transcripts were increased in the AD brains compared to non-dement ed controls but were detected only occasionally in spinal cord and not at all in peripheral nerve. Preliminary data from in situ RT/PCR sugg ests that a large number of cells are expressing. TNF alpha but only a small number are infected with HIV. The finding of elevated TNF alpha associated with increased macrophage activation and decreased IL4 sug gests that the loss of a subset of T cells expressing macrophage regul atory lymphokines such as IL4 and IL10 may explain the observed macrop hage activation seen in the neurological diseases associated with AIDS and play a role in the development of neuronal dysfunction.