Vol. 26 No IL 1 IL 6 IL 8. interleukin IL 6. Key words CCL4 IL Interleukin 6

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1 Vol. 26No GCSF CCL4 IL1IL6IL interleukinil6 4 Key wordsccl4ilinterleukin

2 22 NOx A 77 4 Genzyme Diagnostics FLU 1 3 ml 1 15, BIORAD BioPlex IL1IL2IL4 IL5IL6IL7IL8IL10IL12IL13 IL17 GCSF granulocyte colonystimulating factorgmcsfgranulocyte macrophage colony stimulating factor IFN interferon CCL2 CC motif chemokine 2CCL4CC motif chemokine 4TNFtumor necrosis factor 17 n73n4 # CD1 Cornelia de Lange A2 CD CT 3 1 density MRI 2 1 MERS mild encephalitisencephalopathy with a reversible splenial lesion D 3 n73 n4 1 IL1IL6IL8GCSFIFNCCL2 CCL4TNF GCSF CCL4 2 2 dg T Th1 Th2

3 Vol. 26No. 123 The character, clinical findings, imaging findings and laboratory date of patients with encephalopathy A B C D age 4 y 11 m 7 y 8 y sex M F M F fever seizure consciousness disorder JCS200 JCS200GCSE1V1M1 24 h JCS30GCS 3 E2V1M47 pre medicine PSL past history Cornelia de Lange 2 3 febrile seizure 2 1 febrile seizure 3 2 family history 7 CT edema density edema np edema MRI np EEG RtLt SB IL6serum IL6liquor Hb Plt ASTALT 2, BUNCre CK 4, BS NH PT PTINR APTT FDP ND Ddimer ND

4 24 l l 1The mean and standard deviation of nonencephalopathy groupn73and encephalopathy groupn4in each cytokine and chemokine in the nasal aspirates a nonencephalopathyn73b encephalopathyn4 IFN IL4 3 a IL6TNF IL10 3 bc 4 4 IL2IL7IL10 IL IL6 TNF proinflammatory cytokine 4 6 IL6 TNF proinflammatory cytokine SIRS systemic inflammatory response syndrome

5 Vol. 26No Examination in nonencephalopathy group and encephalopathy group of eight items of the cytokine and chemokine which are rose in the nasal aspirates a IL1pvalue0.118b IL6pvalue0.069c IL8pvalue0.096d GCSFpvalue0.006 e INFpvalue0.089f CCL2pvalue0.408g CCL4pvalue0.034h TNFpvalue , l 2 ASTALTLDH 3 4 Cr 6 ASTALTCPK 4 IL6FerritinTGtriglyceride VAHS virus associated hemophagocytic syndrome

6 26 3IFNIL4 ratio, IL6IL10 ratio and TNFIL10 ratio in the nasal aspirates a IFNIL4pvalue1.00b IL6IL10pvalue0.103c TNFIL10pvalue Cytokine profiles in serum and CSF obtained from patients with encephalopathy a Cytokine profile in serum obtained from patients with encephalopathypgml b Cytokine profile in CSF obtained from patients with encephalopathypgml 11 NOx 12 blood brain barrier IL1IL6IL8

7 Vol. 26No. 127 GCSFIFNCCL2CCL4TNF Patel IL1IL6TNF IL6 14 Fritz IL6TNF IL8 IL10 CCL2CCL3CCL4 IL10 IL6 IL IL10 IL10 Th1 Th17 IL G CSF CCL4 2 IL1IL 6IL8 22 TNF stnfr1 9 IL6 16 GCSF CCL4 GCSF CCL4 17 NOx neurovirulent GCSF CCL4 IL1IL6IL

8 28 2Fukumoto Y, et alserum levels of cytokines and EEG findings in children with influenza associated with mild neurological complications. Brain Dev , Kawashima H, et alprimary biomarkers in cerebral spinal fluid obtained from patients with influenzaassociated encephalopathy analyzed by metabolomics. Int J Neurosci , Watanabe C, et alincreased nitric oxide production and GFAP expression in the brains of influenza ANWS virus infected mice. Neurochem Res , H IL6TNF Ichiyama T, et alcerebrospinal fluid and serum levels of cytokines and soluble tumor necrosis factor receptor in influenza virusassociated encephalopathy. Scand J Infect Dis , Nakamura M, et alclinical application of rapid assay of interleukin6 in influenzaassociated encephalopathy. Dis Markers , Hosoya M, et alcytochrome c and tumor necrosis factoralpha values in serum and cerebrospinal fluid of patients with influenzaassociated encephalopathy. Pediatr Infect Dis J , Kawashima H, et alnitrite and nitrate as a new target of treatments in influenzaassociated encephalopathy. J Pediatr Infect Dis , Ichiyama T, et almatrix metalloproteinase9 and tissue inhibitors of metalloproteinases 1 in influenzaassociated encephalopathy. Pediatr Infect Dis J , Patel JA, et alnasopharyngeal acute phase cytokines in viral upper respiratory infectionimpact on acute otitis media in children. Pediatr Infect Dis J , Fritz RS, et alnasal cytokine and chemokine responses in experimental influenza A virus infectionresults of a placebocontrolled trial of intravenous zanamivir treatment. J Infect Dis , Suzuki S, et alambivalent aspects of interleukin6 in cerebral ischemiainflammatory versus neurotrophic aspects. J Cereb Blood Flow Metab , Babcock AA, et alchemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J Neurosci , Kawashima H, et alnoxnitritenitratein cerebral spinal fluids obtained from patients with influenzaassociated encephalopathy. Neuropediatrics , Kawashima H, et alextraordinary changes in excitatory amino acid levels in cerebrospinal fluid of influenzaassociated encephalopathy of children. Neurochem Res , Mori I, et alolfactory receptor neurons prevent dissemination of neurovirulent influenza A virus into the brain by undergoing virusinduced apoptosis. J Gen Virol 83Pt , Kawada J, et alsystemic cytokine responses in patients with influenzaassociated encephalopathy. J Infect Dis , Ichiyama T, et alcerebrospinal fluid and serum levels of cytokines and soluble tumor necrosis factor receptor in influenza virusassociated encephalopathy. Scand J Infect Dis , 2003

9 Vol. 26No. 129 Cytokine profile of nasal aspirates obtained from patients with influenzaassociated encephalopathy Soken GO, Yasuyo KASHIWAGI, Hisashi KAWASHIMA, Kouji TAKEKUMA Department of Pediatrics, Tokyo Medical University Although mortality from influenzaassociated encephalopathy is lower than before, its sequelae are still high. Therefore, early intervention by treatments is needed. However, diagnosis of earlystage encephalopathy is difficult to predict by conventional laboratory data. Many children with influenzaassociated encephalopathy show neurological symptoms of limbic encephalopathy through suspected olfactory bulb. In order to understand the local immune status, this study assayed 17 cytokines and chemokines in the nasal aspirates from 77 patients, who had influenza withn4and withoutn73encephalopathy. Their cytokine profiles were identical. The levels of GCSF and CCL4 in patients with encephalopathy were significantly higher than those of patients without encephalopathy. Furthermore, the levels of IL1, IL6 and IL8 in patients with encephalopathy were higher than those of patients without encephalopathy. The cytokine profiles in their CSF showed similar tendencies. These findings are useful for better predictions of encephalopathy