Apoptosis under hypercytokinemia is a possible pathogenesis in influenza-associated encephalopathy.
BACKGROUND
Influenza-associated encephalopathy is reported to be frequent in Japan and East Asia. No evaluating markers except interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and no likely pathological mechanism for the disease have yet been elucidated.


METHODS
In this study, influenza-associated encephalopathy was defined by clinical symptoms, and the use of an anti-influenza antibody test and/or influenza antigen detection kits, as well as computed tomography and/or magnetic resonance imaging. The levels of proinflammatory cytokines, acute phase proteins, endothelial markers and cytochrome c were compared in sera from 11 patients with and 42 without encephalopathy.


RESULTS
Cytochrome c concentration in sera from patients with encephalopathy was markedly increased compared with that from patients without encephalopathy and normal controls. Although levels of several other proinflammatory cytokines and acute phase proteins such as TNF-alpha and IL-8 were also elevated in patients with influenza virus infection, the difference between those with and without encephalopathy, though significant, was less dramatic. The mean serum concentration of cytochrome c in 11 patients with encephalopathy, consisting of four deceased, four with and three without residual central nervous system sequelae, was 26.7 +/- 19.5 ng/mL on admission. In contrast, cytochrome c levels in 42 patients without encephalopathy were 0.3 +/- 0.7 ng/mL.


CONCLUSIONS
The present results indicate that cytochrome c is a useful marker to follow patients with influenza-associated encephalopathy and suggest that an apoptosis of cells in several organs including the cerebrum and liver under the influence of hypercytokinemia is a possible mechanism of the disease.
Nunoi
Hiroyuki
H
Department of Pediatrics, Miyazaki Medical College, Miyazaki University, Miyazaki 889-1692, Japan. h-nunoi@fc.miyazaki-med.ac.jp
Mercado
Maria Regina
MR
Mizukami
Tomoyuki
T
Okajima
Kenji
K
Morishima
Tsuneo
T
Sakata
Hiroshi
H
Nakayama
Shinichi
S
Mori
Seiji
S
Hayashi
Masatoshi
M
Mori
Hiromi
H
Kagimoto
Seiichi
S
Kanegasaki
Shiro
S
Watanabe
Keisuke
K
Adachi
Naoto
N
Endo
Fumio
F
D017209:Apoptosis / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D045304:Cytochromes c / Q000097:blood*; D016207:Cytokines; D018792:Encephalitis, Viral / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D007251:Influenza, Human / Q000150:complications*; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D045304:Cytochromes c