Expression of cytokines in brain lesions in subacute sclerosing panencephalitis

Abstract

We analyzed frozen brain specimens from three patients with subacute sclerosing panencephalitis (SSPE) for the presence of interleukin (IL)-1 beta, IL-2, IL-6, tumor necrosis factor (TNF), lymphotoxin (LT), and interferon (IFN)-gamma using immunocytochemical techniques. We detected these cytokines in SSPE brain lesions demonstrating extensive cellular infiltrates, demyelination, and gliosis. Double-label immunocytochemistry, using cell-specific markers, showed that positive immunoreactivity for these cytokines was present on both infiltrating cells and resident brain cells. We also found IL-6, TNF, and IFN-gamma at lower levels in brain tissue from a patient with progressive multifocal leukoencephalopathy. In contrast, normal control brain sections showed no reactivity for any of the cytokines. These findings indicate that IL-1 beta, IL-2, IL-6, TNT, LT, and IFN-gamma may be produced in SSPE lesions and may be involved in the lesion pathogenesis of SSPE.

NFAT4 Is Required for JC Virus Infection of Glial Cells

“…Activation of NFAT4 in HIV-infected patients due to increasing levels of TNF-␣ and IL-2 may be conducive for JCV infection of the CNS. The correlation between increases in TNF-␣ expression and the occurrence of PML in HIVinfected patients supports this idea (25). The possible activation of NFAT by HIV may offer a mechanism for explaining the increased incidence of JCV-induced PML in HIV-infected patients.…”

“…Gene expression profiling and cytokine array data indicate a correlation between the expression of a certain set of gene transcripts and JCV infection (our unpublished observations). Cytokine-profiling data on HIV patients show higher levels of cytokines such as MCP-1 and IL-6 in PML patients than in PML-negative HIV patients (23,25). These data, when combined, may be useful in identifying a profile of genes expressed in response to NFAT4 activity in glial cells.…”

Indoleamine 2,3-Dioxygenase Mediates Cell Type-Specific Anti-Measles Virus Activity of Gamma Interferon

“…After acute infections and vaccinations, IFN-␥ concentrations in the serum are increased (41,43). This cytokine can also be detected in brain lesions of patients suffering from subacute sclerosing panencephalitis (SSPE) (38), a complication developing years after acute MV infection on the basis of a persistent infection of the brain (51,58). Interestingly, the peripheral blood mononuclear cells of most SSPE patients have a reduced capacity to respond to MV infection by producing IFN-␥ (27).…”

Involvement of morbilliviruses in the pathogenesis of demyelinating disease

“…Other theories propose that during the latency period, as MV is thought to be slowly replicating in the brain, viral products in neurons and oligodendroglia slowly increase and eventually lead to cell death and demyelination [89]. Furthermore, infiltration by CD4 þ and CD8 þ T cells and the release of inflammatory cytokines such as IFN-and TNF-has been demonstrated, suggesting that cell-mediated damage to infected cells may play a role [90,91].…”