Effects of zidovudine on murine viral infection-induced peripheral neuropathy and cytokine responses (168.12)

Abstract

Abstract LP-BM5, a murine retroviral isolate, causes a severe acquired immunodeficiency syndrome in C57BL/6 mice, similar to that caused by HIV infection, thus the term murine AIDS (MAIDS). Previously, we have shown that C57BL/6 mice infected with LP-BM5 developed significant hind paw mechanical hypersensitivity, behavioral sign of peripheral neuropathy. To test whether profound inflammatory responses in the nervous system contribute to the development of LP-BM5-induced peripheral neuropathy, we first determined the levels of selected cytokines (IL-1β, IL-6, TNFα, IFNγ, and IL-12) in the lumbar spinal cord and dorsal root ganglia (DRG) by qRT-PCR and in the hind paw skin with FlowCytomix multiplex assay post-LP-BM5 infection (p.i.). In the lumbar spinal cord, mRNA levels of all these cytokines trended upwards over time p.i., whereas in the DRG, IL-1β and IFNγ mRNA levels elevated throughout the time p.i. In the hind paw skin, all cytokines measured (except TNFα that was not detectable) increased transiently and peaked at 4-6 weeks p.i.. Further, administration of the anti-retroviral agent zidovudine (AZT) via drinking water (0.2 mg/ml) significantly reduced LP-BM5-induced mechanical hypersensitivity and cytokine responses in the lumbar spinal cord and DRG at 12 weeks p.i.. Altogether, data indicate that tissue-specific cytokine responses are associated with the development of LP-BM5-induced peripheral neuropathy and these responses can be inhibited by AZT treatment.