Proinflammatory responses in the murine brain after intranasal delivery of cholera toxin: implications for the use of AB toxins as adjuvants in intranasal vaccines.
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.
Armstrong
Michelle E
ME
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.
Lavelle
Ed C
EC
Loscher
Christine E
CE
Lynch
Marina A
MA
Mills
Kingston H G
KH
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D000276:Adjuvants, Immunologic; D018925:Chemokines; D007375:Interleukin-1; D012333:RNA, Messenger; D002772:Cholera Toxin; D051546:Cyclooxygenase 2