Increase of Pro-Inflammatory Cytokine Expression in Non-Demyelinating Early Cerebral Lesions in Nervous Canine Distemper

Abstract

Canine distemper virus (CDV) infection of the central nervous system results in lesions of the gray and white matter. While a biphasic disease process has been discussed for leukoencephalitis with a prominent loss of viral protein expression, polioencephalitis has been associated with virus persistence. Using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), expression of pro- and anti-inflammatory cytokines such as interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF)-alpha, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta were studied in the cerebra of distemper dogs with white matter lesions in the cerebellum. Additionally, cytokine values were correlated with the degree of CDV infection, major histocompatibility complex class II (MHC II) expression, and infiltration of CD4-, CD8-, and CD3epsilon-positive lymphocytes. Cerebral CDV infection was not associated with detectable light microscopic lesions or infiltration of B and T lymphocytes. However, an increasing number of CDV-antigen-positive cells was associated with an upregulation of MHC II antigen. RT-PCR results revealed a significant upregulation of IL-6, IL-8, IL-12, and TNF-alpha in the cerebra of distemper dogs, whereas IL-10 and TGF-beta showed no significant increase. Elevated cytokine values were directly related to the presence of CDV antigen and MHC II upregulation. However, succeeding increases of the latter did not result in an additional proportional elevation of cytokine expression values. In summary, the present study demonstrates the expression of pro-inflammatory cytokines by resident neural cells following CDV infection. Furthermore, the lack of light microscopic changes indicates that additional factors besides cytokines are necessary for the development of a distemper-characteristic neuropathology.