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Proinflammatory Responses in the Murine Brain after Intranasal Delivery of Cholera Toxin: Implications for the Use of AB Toxins as Adjuvants in Intranasal Vaccines
Author(s) -
Michelle E. Armstrong,
Ed C. Lavelle,
Christine E. Loscher,
Marina A. Lynch,
Kingston H. G. Mills
Publication year - 2005
Publication title -
the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/491739
Subject(s) - nasal administration , cholera toxin , proinflammatory cytokine , adjuvant , medicine , chemokine , immunology , immune system , inflammation
Intranasal delivery of vaccines provides an attractive alternative to parenteral delivery, but it requires appropriate mucosal adjuvants. Cholera toxin (CT) is a powerful mucosal adjuvant, but it can undergo retrograde transport to the brain via the olfactory system after intranasal delivery. We demonstrate that intranasal delivery of CT increases the expression of interleukin-1 beta , cyclooxygenase-2, and chemokine messenger RNA in the murine hypothalamus, whereas parenterally delivered CT has little effect. Our findings suggest that CT can induce proinflammatory mediators in the brain when it is administered intranasally but not parenterally, and they raise concerns about the use of AB toxins as adjuvants in intranasal vaccines.

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