Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.

BACKGROUND: Japanese encephalitis virus (JEV), the mosquito-borne flavivirus, annually causes an estimated 35,000-50,000 encephalitis cases and 10,000-15,000 deaths in Asia, and there is no antiviral treatment. The role played by the immune response in determining the outcome of human infection wit...

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Main Authors: Winter, P, Dung, N, Loan, H, Kneen, R, Wills, B, Thu, LT, House, D, White, N, Farrar, J, Hart, C, Solomon, T
פורמט: Journal article
שפה:English
יצא לאור: 2004
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author Winter, P
Dung, N
Loan, H
Kneen, R
Wills, B
Thu, LT
House, D
White, N
Farrar, J
Hart, C
Solomon, T
author_facet Winter, P
Dung, N
Loan, H
Kneen, R
Wills, B
Thu, LT
House, D
White, N
Farrar, J
Hart, C
Solomon, T
author_sort Winter, P
collection OXFORD
description BACKGROUND: Japanese encephalitis virus (JEV), the mosquito-borne flavivirus, annually causes an estimated 35,000-50,000 encephalitis cases and 10,000-15,000 deaths in Asia, and there is no antiviral treatment. The role played by the immune response in determining the outcome of human infection with JEV is poorly understood, although, in animal models of flavivirus encephalitis, unregulated proinflammatory cytokine responses can be detrimental. METHODS: We studied the innate, cellular, and humoral immune responses in 118 patients infected with JEV, of whom 13 (11%) died. RESULTS: Levels of interferon (IFN)- alpha , the proinflammatory cytokine interleukin (IL)-6, and the chemokine IL-8 were all higher in the cerebrospinal fluid (CSF) of the nonsurvivors than of the survivors (P=.04, P=.006, and P=.04, respectively), as were both the IL-6 : IL-4 ratio in CSF (a marker of the balance of pro- and anti-inflammatory cytokines) and the level of the chemokine RANTES (regulated on activation, normally T cell expressed and secreted) in plasma (P=.03). In contrast, levels of immunoglobulin (Ig) M and IgG in CSF and of IgM in plasma were higher in the survivors (P=.035, P=.003, and P=.009, respectively). Levels of IFN- gamma and nitric oxide did not vary with outcome. CONCLUSIONS: During JEV infection, elevated levels of proinflammatory cytokines and chemokines are associated with a poor outcome, but whether they are simply a correlate of severe disease or contribute to pathogenesis remains to be determined.
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spelling oxford-uuid:f03dd2c7-321f-415e-9e75-5764e704a8012022-03-27T11:46:21ZProinflammatory cytokines and chemokines in humans with Japanese encephalitis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f03dd2c7-321f-415e-9e75-5764e704a801EnglishSymplectic Elements at Oxford2004Winter, PDung, NLoan, HKneen, RWills, BThu, LTHouse, DWhite, NFarrar, JHart, CSolomon, T BACKGROUND: Japanese encephalitis virus (JEV), the mosquito-borne flavivirus, annually causes an estimated 35,000-50,000 encephalitis cases and 10,000-15,000 deaths in Asia, and there is no antiviral treatment. The role played by the immune response in determining the outcome of human infection with JEV is poorly understood, although, in animal models of flavivirus encephalitis, unregulated proinflammatory cytokine responses can be detrimental. METHODS: We studied the innate, cellular, and humoral immune responses in 118 patients infected with JEV, of whom 13 (11%) died. RESULTS: Levels of interferon (IFN)- alpha , the proinflammatory cytokine interleukin (IL)-6, and the chemokine IL-8 were all higher in the cerebrospinal fluid (CSF) of the nonsurvivors than of the survivors (P=.04, P=.006, and P=.04, respectively), as were both the IL-6 : IL-4 ratio in CSF (a marker of the balance of pro- and anti-inflammatory cytokines) and the level of the chemokine RANTES (regulated on activation, normally T cell expressed and secreted) in plasma (P=.03). In contrast, levels of immunoglobulin (Ig) M and IgG in CSF and of IgM in plasma were higher in the survivors (P=.035, P=.003, and P=.009, respectively). Levels of IFN- gamma and nitric oxide did not vary with outcome. CONCLUSIONS: During JEV infection, elevated levels of proinflammatory cytokines and chemokines are associated with a poor outcome, but whether they are simply a correlate of severe disease or contribute to pathogenesis remains to be determined.
spellingShingle Winter, P
Dung, N
Loan, H
Kneen, R
Wills, B
Thu, LT
House, D
White, N
Farrar, J
Hart, C
Solomon, T
Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.
title Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.
title_full Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.
title_fullStr Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.
title_full_unstemmed Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.
title_short Proinflammatory cytokines and chemokines in humans with Japanese encephalitis.
title_sort proinflammatory cytokines and chemokines in humans with japanese encephalitis
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