Correlation of tumor necrosis factor levels in the serum and cerebrospinal fluid with clinical outcome in Japanese encephalitis patients

Abstract

To investigate the prognostic role of tumour necrosis factor (TNF) in Japanese encephalitis virus (JEV) infection, we measured the immunoreactive forms of TNF concentrations in the serum and cerebrospinal fluid (CSF) of 47 laboratory-confirmed cases of JE. It was observed that TNF levels were elevated (> 15 pgm/ml) in all the 47 serum samples (range 19.4-923.8 pg/ml), while in 46/47 CSF samples TNF was elevated (range 10.8-376 pg/ml). The mean (SD) TNF levels in the serum of fatal cases was 234.34 pg/ml (304.40) as compared to the mean of 85.31 pg/ml (SD 153.92) in nonfatal cases. Similar observations were also made with respect to the TNF levels in the CSF; the mean of fatal cases was 69.39 pg/ ml (SD 39.00) in contrast to the mean of 62.41 pg/ml (SD 75.25) of nonfatal cases. The increase in TNF levels did not show any correlation to the duration of illness. It was further observed that the mortality rate increased with increasing concentrations of TNF in the serum and CSF. Correlation of laboratory parameters to final outcome revealed that TNF concentrations above 50 pg/ ml in serum correlated significantly (P = .05) with a fatal outcome, whilst high levels of JEV-IgM antibodies (> 500 units) in the CSF correlated with a nonfatal outcome (P = .03). These results suggest that TNF can be used as a possible prognosticator of a fatal outcome in JEV infection.

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

“…Similarly, adoptive transfer of monoclonal antibodies protected mice from lethal encephalitis caused by other flaviviruses, namely JEV [223], SLEV [224], and yellow fever virus [225]. Further, high levels of JEV-specific IgM and IgG in the CSF was linked to virus clearance from the CNS and a better clinical outcome in patients [226,227]. Development of nAbs was also associated with longer survival after intracerebral inoculation of mice with TBEV [208].…”

Immunobiology of Japanese Encephalitis Virus

“…Local immune responses initiated by microglial cells may provide protection against JEV infection of the CNS. However, microglial activation resulting in elevated levels of proinflammatory cytokines (IL-6, TNF-, IL-1 ) and chemokines (IL-8, RANTES, MCP1) in the CSF and plasma may give rise to irreversible neuronal damage and correlates with an increased mortality rate Chen et al, 2010;Ghoshal et al, 2007;Ravi et al, 1997;Saxena et al, 2008;Winter et al, 2004).…”

Acute Encephalitis Syndrome in Adults and Its Correlation with Cytokine Levels in the Serum and Cerebrospinal Fluid

“…It has been well established that during viral infection, release of cytokines and chemokines by host immune cells play an important role in curtailing the infection. The cytokines either directly inhibit the virus or activate the cytotoxic T cells at the site of viral replication (8,9). It has also been shown that cytokines, apart from modulating immune response and inflammatory reaction, also have direct cytotoxic effects, most notable among these being interleukin (IL)-1 and tumor necrosis factor (TNF) (10).…”